Reduction In Left Ventricular Ejection Fraction Research Articles

Effects of the Low-Dose Colchicine Regimen on Left Ventricular Adverse Remodeling and Systolic Function in Acute Myocardial Infarction Patients with Anterior ST-Segment Elevation Undergoing Primary Percutaneous Coronary Intervention: A Randomized Controlled Trial

Background: Inflammation in reperfusion injury results in adverse ventricular remodeling and reduced systolic function. The anti-inflammatory effects of colchicine have shown beneficial effects in cardiovascular disease. Objective: To determine the effects of low-dose colchicine on left ventricular (LV) adverse remodeling and systolic function in acute myocardial infarction with anterior ST-segment elevation (anterior STEMI) patients undergoing primary percutaneous coronary intervention (PPCI). Material and Methods: This prospective, randomized, double-blinded study randomly assigned anterior STEMI patients who underwent PPCI to receive either low-dose colchicine (1mg loading dose followed by 0.5mg daily) or a matching placebo for 30 days in addition to standard therapy. Outcomes included adverse LV remodeling and systolic function, determined by transthoracic echocardiography (TTE) in the first and third month. Result: Enrollment comprised 196 patients, with 92 patients in the colchicine group and 104 patients in the placebo group. Adverse LV remodeling and a decrease in systolic function were observed in both groups. No significant differences in LV remodeling were observed between the colchicine and placebo groups, as indicated by the change in LV end-systolic volume index (LVESVI) at the first month (16.5% vs. 18.25% [p=0.091]) and third month (19.5% vs. 21.5% [p=0.124]). Similar results were found in LV systolic function between the colchicine and placebo groups, with a reduction in LV ejection fraction (LVEF) observed in the first month (6.3% vs. 8.95% [p=0.083]) and third month (9.5% vs. 11.5% [p=0.163]). Diarrhea was the only reported side effect, occurring in 6.5% of patients in the colchicine group. Conclusion: Low-dose colchicine administration in anterior STEMI patients undergoing PPCI did not reduce LV adverse remodeling or systolic function. Keyword: Adverse Remodeling, Colchicine, Reperfusion Injury, STEMI, Systolic Function.

Left Ventricular Function, Congestion, and Effect of Empagliflozin on HeartFailure Risk After MyocardialInfarction.

Empagliflozin reduces the risk of heart failure (HF) hospitalizations but not all-cause mortality when started within 14days of acute myocardial infarction (AMI). This study sought to evaluate the association of left ventricular ejection fraction (LVEF), congestion, or both, with outcomes and the impact of empagliflozin in reducing HF risk post-AMI. In the EMPACT-MI (Trial to Evaluate the Effect of Empagliflozin on Hospitalization for HeartFailure and Mortality in Patients with Acute Myocardial Infarction) trial, patients were randomized within 14days of an AMI complicated by either newly reduced LVEF<45%, congestion, or both, to empagliflozin (10mg daily) or placebo and were followed up for a median of 17.9months. Among 6,522 patients, the mean baseline LVEF was 41 ± 9%; 2,648 patients (40.6%) presented with LVEF<45% alone, 1,483 (22.7%) presented with congestion alone, and 2,181 (33.4%) presented with both. Among patients in the placebo arm of the trial, multivariable adjusted risk for each 10-point reduction in LVEF included all-cause death or HF hospitalization (HR: 1.49; 95%CI: 1.31-1.69; P< 0.0001), first HF hospitalization (HR: 1.64; 95%CI: 1.37-1.96; P< 0.0001), and total HF hospitalizations (rate ratio [RR]: 1.89; 95%CI: 1.51-2.36; P< 0.0001). The presence of congestion was also associated with a significantly higher risk for each of these outcomes (HR: 1.52, 1.94, and RR: 2.03, respectively). Empagliflozin reduced the risk for first (HR: 0.77; 95%CI: 0.60-0.98) and total (RR: 0.67; 95%CI: 0.50-0.89) HF hospitalizations, irrespective of LVEF or congestion, or both. The safety profile of empagliflozin was consistent across baseline LVEF and irrespective of congestion status. In patients with AMI, the severity of left ventricular dysfunction and the presence of congestion was associated with worse outcomes. Empagliflozin reduced first and total HF hospitalizations across the range of LVEF with and without congestion. (Trial to Evaluate the Effect of Empagliflozin on Hospitalization for HeartFailure and Mortality in Patients with Acute Myocardial Infarction [EMPACT-MI]; NCT04509674).

Left atrial reservoir longitudinal strain and its incremental value to the left ventricular global longitudinal strain in predicting anthracycline-induced cardiotoxicity.

Left ventricular global longitudinal strain (LVGLS) has been recommended by current guidelines for diagnosing anthracycline-induced cardiotoxicity. However, little is known about the early changes in left atrial (LA) morphology and function in this population. Our study aimed to evaluate the potential usefulness of LA indices and their incremental value to LVGLS with three-dimensional echocardiography (3DE) in the early detection of subclinical cardiotoxicity in patients with lymphoma receiving anthracycline. A total of 80 patients with diffuse large B-cell lymphoma who received six cycles of anthracycline-based treatment were enrolled. Echocardiography was performed at baseline (T0), after four cycles (T1), and after the completion of six cycles of chemotherapy (T2). Left ventricular ejection fraction (LVEF), LVGLS, LA volumes, LA emptying fraction (LAEF), LA active emptying fraction (LAAEF), and LA reservoir longitudinal strain (LASr) were quantified with 3DE. Left atrioventricular global longitudinal strain (LAVGLS) was calculated as the sum of peak LASr and the absolute value of peak LVGLS (LAVGLS=LASr+|LVGLS|). LV cardiotoxicity was defined as a new LVEF reduction by ≥10 percentage points to an LVEF of ≤50%. Fourteen (17.5%) patients developed LV cardiotoxicity at T2. LA volumes, LAEF, and LAAEF remained stable over time. Impairment of LASr (28.35±5.03vs. 25.04±4.10, p<.001), LVGLS (-22.77±2.45vs. -20.44±2.62, p<.001), and LAVGLS (51.12±5.63vs. 45.61±5.22, p<.001) was observed by the end of the fourth cycle of chemotherapy (T1). Statistically significant declines in LVEF (61.30±4.73vs. 57.08±5.83, p<.001) were only observed at T2. The relative decrease in LASr (ΔLASr), LVGLS (ΔLVGLS), and LAVGLS (ΔLAVGLS) from T0 to T1 were predictors of LV cardiotoxicity. A ΔLASr of>19.75% (sensitivity, 71.4%; specificity, 87.9%; area under the curve (AUC),.842; p<.001), a ΔLVGLS of>13.19% (sensitivity, 78.6%; specificity, 74.2%; AUC,.763; p<.001), and a ΔLAVGLS of>16.80% (sensitivity, 78.6%; specificity, 93.9%; AUC,.905; p<.001) predicted subsequent LV cardiotoxicity at T2, with the AUC of ΔLAVGLS significantly larger than that of ΔLVGLS (.905vs..763, p=.027). Compared to ΔLVGLS, ΔLAVGLS showed improved specificity (93.9%vs. 74.2%, p=.002) and maintained sensitivity in predicting LV cardiotoxicity. LASr could predict anthracycline-induced LV cardiotoxicity with excellent diagnostic performance. Incorporating LASr into LVGLS (LAVGLS) led to a significantly improved specificity and maintained sensitivity in predicting LV cardiotoxicity.

Prognostic and functional importance of both overt and subclinical left ventricular systolic dysfunction in systemic sclerosis

ObjectivesTo quantify the frequency and clinical implications of systemic sclerosis (SSc)-associated left ventricular function (LV) impairment. MethodsAustralian Scleroderma Cohort Study participants meeting ACR/EULAR criteria for SSc with ≥1 echocardiographic LVEF measurement were included. Overt LV dysfunction was indicated by reduced LV ejection fraction (LVEF) and subclinical LV dysfunction was measured using impaired LV global longitudinal strain (LV-GLS>-16%). Those with secondary causes of LV dysfunction (myocardial ischaemia, valvulopathy and pulmonary arterial hypertension) were excluded. Chi-squared tests, two-sample t-tests or Wilcoxon rank-sum tests were used for between-group comparison as appropriate. Generalised estimating equations(GEE) were used to model longitudinal data. Kaplan-Meier and Cox proportional hazard models were used for survival analyses. ResultsOf 1141 participants with no co-morbid cardiac disease, 2.4% ever recorded a LVEF<50%, while only 0.6% ever recorded a LVEF≤40%. LV-GLS data were available for 90% of participants at one centre (n=218). Impaired LV-GLS was detected in 21% despite LVEF≥50%. Those with a LVEF<50% were more frequently male (p=0.01) with dcSSc (p<0.01), higher inflammatory markers (p<0.02) and skeletal muscle disease (p<0.05). In multivariable analyses, recording a LVEF<50% was associated with increased mortality (HR2.3, 95%CI1.0-4.8, p=0.04). Impaired LV-GLS was also associated with poorer survival in univariable analyses (HR3.4, 95%CI1.0-11.8, p=0.05). Those with a LVEF<50% more frequently recorded WHO Class III/IV dyspnoea (OR3.5, 95%CI1.6-7.7, p<0.01), with shorter six-minute walk distance (p=0.01), higher Health Assessment Questionnaire-Disability Index scores (p<0.01) and lower Short Form-36 Physical Component Summary scores (p=0.02). Increased dyspnoea (WHO Class III/IV dyspnoea; OR3.6, 95%CI1.4-9.2, p<0.01) was also seen in those with impaired LV-GLS. ConclusionsBoth overt and subclinical SSc-associated LV dysfunction are associated with worse survival and impaired physical function. The frequency of abnormal LV-GLS in those with consistently normal LVEF suggests an under-appreciated burden of subtle LV systolic dysfunction in SSc that has a significant impact on patient symptomatology.

Aetiology and predictors of major bleeding events in patients with heart failure with reduced ejection fraction undergoing percutaneous coronary intervention

ObjectivesWe sought to determine the relationship between the degree of left ventricular ejection fraction (LVEF) impairment and the frequency and type of bleeding events after percutaneous coronary intervention (PCI).DesignThis was...

O163: CABG versus PCI in Heart Failure with Reduced Ejection Fraction Patients: A Systematic Review &amp; Meta-analysis Stratified by Left Ventricular Ejection Fraction

Abstract Background Comparing coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) in patients with heart failure with reduced ejection fraction (HFrEF) remains controversial within the literature. The current meta-analysis aimed to compare CABG and PCI in HFrEF patients regarding mortality and long-term survival, repeat revascularization, new postoperative myocardial infarction (MI) and stroke, stratified by the degree of LVEF reduction. Methods In a systematic review, a comprehensive literature search was conducted on multiple electronic databases using strict search terms. Twenty studies met the set inclusion/exclusion criteria. Meta-analysis of extracted data was conducted using the R-studio and STATA software. Furthermore, the aforementioned study endpoints were stratified by the degree of left ventricular ejection fraction (LVEF) reduction into severe (&amp;lt;35%), moderate (&amp;lt;40%) and mild (&amp;lt;50%). Results Data from 25,031 HFrEF patients was analysed, out of which 12,957 (52%) underwent CABG and 12,074 (48%) received PCI. Long-term survival was significantly higher in the severe (&amp;lt;35%) and mildly (&amp;lt;50%) reduced LVEF groups, with no significant different found in the moderately (&amp;lt;40%) reduced LVEF cohort. However, all 3 groups significantly favoured CABG in terms of need for revascularization, but no difference in stroke incidence was found. As for postoperative MI, this followed the same trend as survival. No evidence of significant heterogeneity or publication bias was found. Conclusion CABG yields more favourable results than PCI in HFrEF patients. Further stratifying the clinical outcomes measured by the degree of LVEF reduction sheds light on the importance of risk stratification of patients to optimise results.

Hemodialysis Patients with High-Flow Arteriovenous Fistulas: An Evaluation of the Impact on Cardiac Function.

: Patients undergoing hemodialysis often experience changes in cardiac function when they have a high-flow arteriovenous fistula (AVF). This study aimed to assess the effect of high-flow AVFs on cardiac function in patients undergoing hemodialysis. : A longitudinal study was conducted on hemodialysis patients with high-flow AVFs. Echocardiographic parameters, such as left ventricular ejection fraction (LVEF), left atrial diameter (LAD), left ventricular end-diastolic dimension (LVEDD), right ventricular end-diastolic dimension (RVEDD), inferior vena cava diameter (IVCD), systolic blood pressure, and diastolic blood pressure, were measured and compared before and after AVF creation. : One hundred hemodialysis patients with high-flow AVFs (mean age: 55.95±13.39 years, mean body mass index: 24.71±3.43 kg/m²) were studied. LVEF significantly decreased (51.10%±5.39% to 47.50%±5.79%), while LAD, LVEDD, and IVCD significantly increased after AVF creation (P<0.05). Systolic (132.49±16.42 mmHg to 146.60±17.43 mmHg) and diastolic (79.98±8.40 mmHg to 83.33±9.68 mmHg) blood pressure substantially rose post-fistularization (P<0.001). Notably, LVEF reduction was more significant in brachio-cephalic AVFs (46.29%±4.24%) compared to distal radio-cephalic or snuffbox AVFs (49.17%±7.15%) (P=0.014). : High-flow AVFs can significantly affect echocardiographic parameters in hemodialysis patients, thereby increasing the risk of cardiac failure. Close cardiac monitoring may be necessary for early intervention. Distal AVFs may be preferable in patients with decreased cardiac function.

Retirada del tratamiento farmacológico en pacientes respondedores a terapia de resincronización cardiaca: justificación y diseño del ensayo clínico REMOVE

Introduction and objectivesCardiac resynchronization therapy (CRT) is an effective treatment for patients with nonischemic dilated cardiomyopathy associated with left bundle branch block (LBBB). In these patients, the device can normalize left ventricular ejection fraction (LVEF). Nevertheless, it remains unclear whether CRT responders still require neurohormonal blockers. The aim of this study is to determine the long-term safety of withdrawing drug therapy in these patients. MethodsThe REMOVE trial (NCT05151861) is a prospective, multicenter, open-label and randomized 1:1 study designed to assess the effect of withdrawing neurohormonal blockers in patients with nonischemic dilated cardiomyopathy associated with left bundle branch block who recovered LVEF after CRT. The study will include a 12-month follow-up with the option to continue into the follow-up extension phase for up to 24 months. The primary endpoint is the recurrence of cardiomyopathy defined as any of the following criteria: a) a reduction in LVEF >10% (provided the LVEF is <50%); b) a reduction in LVEF >10% accompanied by an increase >15% in the indexed end-systolic volume relative to the previous value and in a range higher than the normal values, or c) decompensated heart failure requiring intravenous diuretic administration. In patients meeting the primary endpoint, drug therapy will be restarted. ConclusionsThe results of this study will help to enhance our understanding of CRT superresponders, a specific group of patients.

The Association Between Ascending Aortic and Left Ventricular Dimensions in Patients After Aortic Valve Replacement.

Aortic valve replacement (AVR) is often recommended for patients with severe aortic stenosis or chronic aortic regurgitation. These conditions result in remodeling of the left ventricle, including increased interstitial fibrosis that may persist even after AVR. These structural changes impact left ventricular (LV) mechanics, causing compromised LV diameter to occur earlier than reduced LV ejection fraction (LVEF). The aim of this study was to examine the effect of left ventricular end-diastolic diameter (LVEDD) and its role in aortic expansion one year after AVR. Sixty-three patients who underwent AVR were evaluated. All patients underwent standard transthoracic echocardiography, which included measurements of the ascending aorta, aortic root, LVEF, and LVEDD before the surgery and one year postoperatively. Correlations between these variables were calculated. All patients underwent AVR with either a mechanical or biological prosthetic aortic valve. Following AVR, there was a significant decrease in the dimensions of the ascending aorta and aortic root (both P=0.001). However, no significant changes were observed in LVEDD and LVEF. Correlations were found between the preoperative ascending aortic size and the preoperative and one-year postoperative LVEDD (r=0.419, P=0.001 and r=0.320, P=0.314, respectively). Additionally, there was a correlation between the postoperative ascending aortic size and the preoperative and one-year postoperative LVEDD (r=0.320, P=0.003 and r=0.136, P=0.335, respectively). The study findings demonstrate a significant correlation between the size of the aortic root and ascending aorta, before and after AVR. Additionally, a notable correlation was observed between postoperative LVEDD and the size of the aortic root.

Subclinical myocardial damage after anthracycline chemotherapy in Japanese patients with breast cancer

BackgroundData on the incidence, timing, and severity of myocardial damage after anthracycline-based chemotherapy (AC) in Japanese patients with breast cancer are limited. MethodWe evaluated cancer therapy-related cardiac dysfunction (CTRCD) in Japanese women with breast cancer (n = 51) after the first AC according to the definitions of the 2022 European Society of Cardiology onco-cardiology guideline, including assessment of high-sensitivity troponin I (TnI) and B-type natriuretic peptide (BNP) levels. ResultsCTRCD was detected in 67 % of the patients (3.9 %, 7.8 %, 9.8 %, 43 %, 37 %, 22 %, 20 %, and 9.8 % of patients at 1 week and 1, 2, 3, 6, 9, 12, and 15 months post-AC, respectively) without significant left ventricular ejection fraction reduction (<50 %) and heart failure. Elevated TnI levels (>26 pg/mL) were found in 43 % of patients, and elevated BNP levels (≥35 pg/mL) were observed in 22 % of patients during the follow-up period. ConclusionsApproximately two-thirds of the Japanese patients in this study experienced CTRCD, which was frequently observed at 3 or 6 months post-AC. However, all patients with CTRCD were diagnosed with mild asymptomatic CTRCD. Although, these patients were diagnosed with mild asymptomatic CTRCD, careful long-term follow-up will be required.

Drug Interactions in the Treatment of Chronic Heart Failure: Analysis of Clinical Guidelines

Background. According to Russian epidemiological studies, the prevalence of chronic heart failure (CHF) in the general population is high and amounts to 7–10%. Therapy of any disease, and especially chronic disease, is associated with the prescription of drugs. With the development of evidence-based medicine and implementation of its achievements in real clinical practice all over the world there is an increase in the number of prescribed drugs. This explains the high relevance of the problem of drug-drug interactions. Aims — analysis of interactions of drugs recommended for prescription to patients suffering from CHF. Methods. Based on the Clinical Guidelines (CG), all possible interdrug interactions of recommended medicinal products were analysed. Information on potential drug-drug interactions was obtained from the specialised website Drugs.com. Know more. Be sure (https://www.drugs.com/interactions/list/). Results. ACE inhibitors / ARA II / valsartan+sacubitril, beta-adrenoblockers and aldosterone antagonists are recommended as part of combination therapy for treatment according to CG for all patients with symptomatic heart failure (class II–IV) and reduced LV ejection fraction 40%. Amiodarone, verapamil and diltiazem are among the drugs not recommended for use in patients with the diagnosis of CHF. Also, according to clinical guidelines, HMG-CoA reductase inhibitors (atorvastatin, lovastatin, pitavastatin, rosuvastatin, simvastatin, fluvastatin), direct renin inhibitors (heparin), COX-2 inhibitors (parecoxib, polmacoxib, celecoxib, etoricoxib) are among the unrecommended drugs in chronic heart failure.For ACE inhibitors, no adverse effects from interaction with beta-blockers have been identified. This combination is widely used and recommended by the CG. According to the “Major” type for ACE inhibitors with drugs indicated for use in CHF according to CG, 4 potential interactions were identified: with valsartan-sacubitril; angiotensin II receptor antagonists; with aldosterone antagonist (spironolactone); with loop and thiazide diuretics. Therefore, the appointment of angiotensin II receptor antagonists is carried out in case of ineffectiveness of initial therapy with ACE inhibitors, when changing the treatment tactics. These drugs are not used in combination with each other due to the risk of hyperkalemia. The prescription and use of diuretics while taking ACE inhibitors should be controlled by a physician also due to the risk of hyperglycaemia. In Moderate type, potential interactions with dapagliflozin, eplerenone, cardiac glycosides and heparin have been identified for ACE inhibitors. For beta-blockers, no potential Major-type interactions were identified with drugs from CG. Combinations with dapagliflozin, loop and thiazide diuretics, cardiac glycosides, spironolactone and ivabradine require special attention. It is recommended to avoid the combination of beta-blockers with valsartan. Of the recommended angiotensin II receptor antagonists, no risk of potential interactions with beta-blockers has been identified for candesartan and losartan.

Renal function improvement correlates with 3D echocardiographic findings: Effect of surgical mitral valve repair.

The association between surgical treatment of mitral regurgitation (MR) and renal function is not sufficiently well-known. We tried to evaluate renal function before and after the procedure of surgical mitral valve repair (SMVR) in degenerative severe MR. Patients with primary severe (4+) MR and normal left ventricular ejection fraction (LVEF) that underwent SMVR, examined by a cutting-edge 3-dimensional (3D) echocardiographic probe were enrolled in this study. We took three CKD-EPI equations to measure estimated glomerular filtration rate (eGFR) before SMVR and shortly before patients discharge. A total of 40 patients with baseline lower mean eGFR were evaluated. Measurements substantiated statistically significant improvements in eGFR (p < 0.001), multivariable linear regression modeling indicating prominent associations between increase in eGFR and decrease of MR (p = 0.003), decline of pulmonary arterial systolic pressure (p = 0.018), as well as increment of forward stroke volume (p = 0.02), in spite of LVEF reduction, left ventricular global longitudinal strain worsening and left atrial ejection fraction impairment. Renal function improves after SMVR in patients with degenerative significant MR and preserved LVEF, regardless of cardiac functional worsening.

Deletion of DWORF does not affect cardiac function in aging and in PLN-R14del cardiomyopathy.

The phospholamban (PLN) pathogenic gene variant p.Arg14del causes cardiomyopathy, which is characterized by perinuclear PLN protein clustering and can lead to severe heart failure (HF). Elevated expression of dwarf open reading frame (DWORF), a protein counteracting the function of PLN in the sarcoplasmic reticulum (SR), can delay disease progression in a PLN-R14del mouse model. Here, we evaluated whether deletion of DWORF (DWORF-/-) would have an opposite effect and accelerate age-dependent disease progression in wild-type (WT) mice and mice with a pathogenic PLN-R14del allele (R14Δ/+). We show that DWORF-/- mice maintained a normal left ventricular ejection fraction (LVEF) during aging and no difference with WT control mice could be observed up to 20 mo of age. R14Δ/+ mice maintained a normal cardiac function until 12 mo of age, but at 18 mo of age, LVEF was significantly reduced as compared with WT mice. Absence of DWORF did neither accelerate the R14Δ/+-induced reduction in LVEF nor enhance the increases in gene expression of markers related to cardiac remodeling and fibrosis and did not exacerbate cardiac fibrosis caused by the R14Δ/+ mutation. Together, these results demonstrate that absence of DWORF does not accelerate or exacerbate PLN-R14del cardiomyopathy in mice harboring the pathogenic R14del allele. In addition, our data indicate that DWORF appears to be dispensable for cardiac function during aging.NEW & NOTEWORTHY Although DWORF overexpression significantly delayed heart failure development and strongly prolonged life span in PLN-R14del mice, the current study shows that deletion of DWORF does not accelerate or exacerbate PLN-R14del cardiomyopathy in mice harboring the pathogenic R14del allele. In addition, DWORF appears to be dispensable for cardiac function during aging. Changes in DWORF gene expression are therefore unlikely to contribute to the clinical heterogeneity observed in patients with PLN-R14del cardiomyopathy.

Non-dilated left ventricular cardiomyopathy vs. dilated cardiomyopathy: clinical background and outcomes.

Non-dilated left ventricular cardiomyopathy (NDLVC) was proposed as a new category of cardiomyopathy that included patients with non-left ventricular (LV) dilatation, LV wall motion abnormality, or LV scar. However, the clinical background and event rates of NDLVC were unclear. The aim of this study was to examine the characteristics and event rates of patients with NDLVC and reduced LV ejection fraction (NDLVC-REF) in comparison with those with dilated cardiomyopathy (DCM). We retrospectively included 363 patients with newly diagnosed non-ischaemic cardiomyopathy and reduced LV ejection fraction (<50%) between December 2004 and January 2018. Patients who did not have LV dilatation (LV dimension index of ≦31mm/m2 in men and ≦34mm/m2 in women) were categorized as NDLVC-REF (n=80, 22.2%), and the remaining patients were categorized as DCM. Cardiac events were defined as sudden cardiac death and rehospitalization for heart failure. Patients with NDLVC-REF had a higher prevalence of atrial fibrillation and a higher LV ejection fraction than those with DCM at baseline. LV ejection fraction was higher and LV end-diastolic diameter was smaller in patients with NDLVC-REF than in those with DCM at all time points after diagnosis. During the median follow-up period of 68.8months (interquartile range: 33.0-93.7months), 44 patients experienced cardiac events. The Kaplan-Meier curves showed no significant differences in the probability of cardiac events among NDLVC-REF and DCM patients (P=0.349). However, patients with NDLVC-REF and LV dilatation after diagnosis (14%) had a higher risk of cardiac events than those with NDLVC-REF without LV dilatation (P=0.049). There was no significant difference in the incidence of cardiac events between NDLVC-REF and DCM. Among NDLVC-REF patients, 18% of patients who showed LV dilatation after diagnosis had poor outcomes. Therefore, both NDLVC-REF and DCM patients may require equivalent attention to follow-up and regular assessment of LV function.

Identifying left ventricular dysfunction using prospective electrocardiogram-triggered coronary computed tomography angiography

PurposeCoronary computed tomography angiography (CCTA) is an important non-invasive tool for the assessment of coronary artery disease and the delivery of information incremental to coronary anatomy. CCTA measured left ventricular (LV) mid-diastolic volume (LVMDV) and LV mass (LVMass) have important prognostic information but the utility of prospectively ECG-triggered CCTA to predict reduced left ventricular ejection fraction (LVEF) is unknown. The objective of this study was to determine if indexed LVMDV (LVMDVi) and the LVMDV:LVMass ratio on CCTA can identify patients with reduced LVEF. Materials/methods8179 patients with prospectively ECG-triggered CCTA between November 2014 and December 2019 were reviewed. A subset derivation cohort of 4352 healthy patients was used to define normal LVMDVi and LVMDV:LVMass. Sex-specific thresholds were tested in a validation cohort of 1783 patients, excluded from the derivation cohort, with cardiac disease and known LVEF. The operating characteristics for 1 SD above the mean were tested for the identification of abnormal LVEF, LVEF≤35 ​% and ≤30 ​%. ResultsThe derivation cohort had a mean LVMDVi of 61.0 ​± ​13.7 ​mL/m2 and LVMDV:LVMass of 1.11 ​± ​0.24 ​mL/g. LVMDVi and LVMDV:LVMass were both higher in patients with reduced LVEF than those with normal LVEF (98.8 ​± ​40.8 ​mL/m2 vs. 63.3 ​± ​19.7 ​mL/m2, p ​< ​0.001, and 1.32 ​± ​0.44 ​mL/g vs. 1.05 ​± ​0.28 ​mL/g, p ​< ​0.001). Both mean LVMDVi and LVMDV:LVMass increased with the severity of LVEF reduction. Sex-specific LVMDVi thresholds were 79 ​% and 80 ​% specific for identifying abnormal LVEF in females (LVMDVi ​≥ ​69.9 ​mL/m2) and males (LVMDVi ​≥ ​78.8 ​mL/m2), respectively. LVMDV:LVMass thresholds had high specificity (87 ​%) in both females (LVMDVi:LVMass ​≥ ​1.39 ​mL/g) and males (LVMDVi:LVMass ​≥ ​1.30 ​mL/g). ConclusionOur study provides reference thresholds for LVMDVi and LVMDV:LVMass on prospectively ECG-triggered CCTA, which may identify patients who require further LV function assessment.

Clinical characteristics and outcome of end stage hypertrophic cardiomyopathy: Role of age and heart failure phenotypes

BackgroundA minority of patients with hypertrophic cardiomyopathy (HCM) presents advanced heart failure (HF) during their clinical course, in the context of left ventricular (LV) remodeling with reduced LV ejection fraction (LVEF), or of severe diastolic dysfunction without impaired LVEF. Aim of this study was to describe a multicentric end stage (ES) HCM population and analyze clinical course and outcome among its different phenotypes. MethodsData of all HCM patients from 7 Italian referral centres were retrospectively evaluated. ES was diagnosed in presence of: LVEF <50% (ES-rEF) or NYHA functional class ≥II with severe diastolic dysfunction (ES-pEF). Outcomes were: HCM-related and all-cause mortality; combined arrhythmic events; advanced HF treatments. ResultsStudy population included 331 ES patients; 87% presented ES-rEF and 13% ES-pEF. At ES recognition, patients with ES-pEF were more commonly females, had more frequently NYHA III/IV, atrial fibrillation and greater maximal LV wall thickness. Over a median follow-up of 5.6 years, 83 (25%) patients died, 46 (15%) experienced arrhythmic events and (26%) 85 received advanced HF treatments. Incidence of HCM-related and all-cause mortality, and of combined arrhythmic events did not differ in ES-pEF and ES-rEF patients, but ES-pEF patients were less likely to receive advanced HF treatments. Older age at ES recognition was an independent predictor of increased HCM-related mortality (p = 0.01) and reduced access to advanced HF treatments (p < 0.0001). ConclusionsTwo different HCM-ES phenotypes can be recognized, with ES-pEF showing distinctive features at ES recognition and receiving less frequently advanced HF treatments. Older age at ES recognition has a major impact on outcomes.

Sequential neoadjuvant chemotherapy using pegylated liposomal doxorubicin and cyclophosphamide followed by taxanes with complete trastuzumab and pertuzumab treatment for HER2-positive breast cancer: A phase II single-arm study.

Despite cardiotoxicity overlap, the trastuzumab/pertuzumab and anthracycline combination remains crucial due to significant benefits. Pegylated liposomal doxorubicin (PLD), a less cardiotoxic anthracycline, was evaluated for efficacy and cardiac safety when combined with cyclophosphamide and followed by taxanes with trastuzumab/pertuzumab in human epidermal growth factor receptor-2 (HER2)-positive early breast cancer (BC). In this multicenter, phase II study, patients with confirmed HER2-positive early BC received four cycles of PLD (30-35 mg/m2) and cyclophosphamide (600 mg/m2), followed by four cycles of taxanes (docetaxel, 90-100 mg/m2 or nab-paclitaxel, 260 mg/m2), concomitant with eight cycles of trastuzumab (8 mg/kg loading dose, then 6 mg/kg) and pertuzumab (840 mg loading dose, then 420 mg) every 3 weeks. The primary endpoint was total pathological complete response (tpCR, ypT0/is ypN0). Secondary endpoints included breast pCR (bpCR), objective response rate (ORR), disease control rate, rate of breast-conserving surgery (BCS), and safety (with a focus on cardiotoxicity). Between May 27, 2020 and May 11, 2022, 78 patients were treated with surgery, 42 (53.8%) of whom had BCS. After neoadjuvant therapy, 47 [60.3%, 95% confidence interval (95% CI), 48.5%-71.2%] patients achieved tpCR, and 49 (62.8%) achieved bpCR. ORRs were 76.9% (95% CI, 66.0%-85.7%) and 93.6% (95% CI, 85.7%-97.9%) after 4-cycle and 8-cycle neoadjuvant therapy, respectively. Nine (11.5%) patients experienced asymptomatic left ventricular ejection fraction (LVEF) reductions of ≥10% from baseline, all with a minimum value of >55%. No treatment-related abnormal cardiac function changes were observed in mean N-terminal pro-BNP (NT-proBNP), troponin I, or high-sensitivity troponin. This dual HER2-blockade with sequential polychemotherapy showed promising activity with rapid tumor regression in HER2-positive BC. Importantly, this regimen showed an acceptable safety profile, especially a low risk of cardiac events, suggesting it as an attractive treatment approach with a favorable risk-benefit balance.

Potential Underestimation of Left Ventricular Mechanical Dyssynchrony in Dyssynchrony and Outcomes Assessment.

Left ventricular (LV) mechanical dyssynchrony (LVMD) is fundamental to the progression of heart failure and ventricular remodeling. The status of LVMD in different patterns of bundle branch blocks (BBB) is unclear. In this study, we analyzed the relationship between LVMD and left ventricular systolic dysfunction using real-time three-dimensional echocardiography (RT-3DE). RT-3DE and conventional two-dimensional echocardiography were performed on 68 patients with left bundle branch block (LBBB group), 106 patients with right bundle branch block (RBBB group), and 103 patients without BBB (Normal group). The RT-3DE data sets provided time-volume analysis for global and segmental LV volumes. The LV systolic dyssynchrony index (LVSDI) was calculated using the standard deviation (SD) and maximal difference (Dif) of time to minimum segmental volume (tmsv) for LV segments adjusted by the R-R interval. LVMD was considered if the LVSDI (Tmsv-16-SD) was greater than or equal to 5%. LVSDI is negatively and significantly correlated with left ventricular ejection fraction (LVEF), but not with BBB or QRS duration. The proportion of LVMD in the LBBB, RBBB, and Normal group was 30.88%, 28.30%, and 25.24%, respectively, and there was no significant difference. In dilated cardiomyopathy, LVMD is more closely related to LVEF reduction than QRS morphology and duration.

Virtual pacing of a patient's digital twin to predict left ventricular reverse remodelling after cardiac resynchronization therapy.

Identifying heart failure (HF) patients who will benefit from cardiac resynchronization therapy (CRT) remains challenging. We evaluated whether virtual pacing in a digital twin (DT) of the patient's heart could be used to predict the degree of left ventricular (LV) reverse remodelling post-CRT. Forty-five HF patients with wide QRS complex (≥130 ms) and reduced LV ejection fraction (≤35%) receiving CRT were retrospectively enrolled. Echocardiography was performed before (baseline) and 6 months after CRT implantation to obtain LV volumes and 18-segment longitudinal strain. A previously developed algorithm was used to generate 45 DTs by personalizing the CircAdapt model to each patient's baseline measurements. From each DT, baseline septal-to-lateral myocardial work difference (MWLW-S,DT) and maximum rate of LV systolic pressure rise (dP/dtmax,DT) were derived. Biventricular pacing was then simulated using patient-specific atrioventricular delay and lead location. Virtual pacing-induced changes ΔMWLW-S,DT and ΔdP/dtmax,DT were correlated with real-world LV end-systolic volume change at 6-month follow-up (ΔLVESV). The DT's baseline MWLW-S,DT and virtual pacing-induced ΔMWLW-S,DT were both significantly associated with the real patient's reverse remodelling ΔLVESV (r = -0.60, P < 0.001 and r = 0.62, P < 0.001, respectively), while correlation between ΔdP/dtmax,DT and ΔLVESV was considerably weaker (r = -0.34, P = 0.02). Our results suggest that the reduction of septal-to-lateral work imbalance by virtual pacing in the DT can predict real-world post-CRT LV reverse remodelling. This DT approach could prove to be an additional tool in selecting HF patients for CRT and has the potential to provide valuable insights in optimization of CRT delivery.

Anthracycline-related cardiotoxicity in patients with breast cancer harboring mutational signature of homologous recombination deficiency (HRD)

The BRCA proteins play a key role in the homologous recombination (HR) pathway. Beyond BRCA1/2, other genes are involved in the HR repair (HRR). Due to the prominent role in the cellular repair process, pathogenic or likely pathogenic variants (PV/LPVs) in HRR genes may cause inadequate DNA damage repair in cardiomyocytes. This was a multicenter, hospital-based, retrospective cohort study to investigate the heart toxicity from anthracycline-containing regimens (ACRs) in the adjuvant setting of breast cancer (BC) patients carrying germline BRCA PV/LPVs and no-BRCA HRR pathway genes. The left ventricular ejection fraction (LVEF) was assessed using cardiac ultrasound before starting ACR therapy and at subsequent time points according to clinical indications. Five hundred and three BC patients were included in the study. We predefined three groups: (i) BRCA cohort; (ii) no-BRCA cohort; (iii) variant of uncertain significance (VUS)/wild-type (WT) cohort. When baseline (T0) and post-ACR (T1) LVEFs between the three cohorts were compared, pre-treatment LVEF values were not different (BRCA1/2 versus HRR-no-BRCA versus VUS/WT cohort). Notably, during monitoring (T1, median 3.4 months), patients carrying BRCA or HRR no-BRCA germline pathogenic or likely pathogenic variants showed a statistically significant reduction of LVEF compared to baseline (T0). To assess the relevance of HRR on the results, we included the analysis of the subgroup of 20 BC patients carrying PV/LPVs in other genes not involved in HRR, such as mismatch repair genes (MUTYH, PMS2, MSH6). Unlike HRR genes, no significant differences in T0-T1 were found in this subgroup of patients. Our data suggest that deleterious variants in HRR genes, leading to impaired HR, could increase the sensitivity of cardiomyocytes to ACR in early BC patients. In this subgroup of patients, other measurements, such as the global longitudinal strain, and a more in-depth assessment of risk factors may be proposed in the future to optimize cardiovascular risk management and improve long-term survival.