Abstract
Background
Heart failure with preserved ejection fraction (HFpEF) represents nowadays the most frequent presentation of heart failure (HF) in patients aged > 65 years. The underlying reason ...for the failure of the vast majority of randomized controlled trials (RCTs) in HFpEF patients has been identified in the heterogeneity of pathophysiology and clinical phenotype of this clinical syndrome. Coronary microvascular dysfunction (CMD) represents one among various pathophysiological mechanisms, together with pulmonary vascular disease, pericardial restraint, impaired chronotropic reserve and abnormal autonomic tone. Whether CMD-HFpEF endotype differs from the others in terms of echocardiographic parameters and clinical outcomes is still a matter of debate. Therefore, a systematic review and meta-analysis were performed in order to compare HFpEF populations with or without CMD in terms of echocardiographic features and clinical outcomes.
Methods
We searched for articles published in PubMed, Scopus and Wiley comparing HFpEF population with or without CMD up to 1st September 2022. Observational studies, reporting echocardiographic parameters mentioned in HFA-PEFF score and/or clinical time to event data, were included. E/e’ ratio, left atrial volume index (LAVi) and left ventricular mass index (LVMi) constituted our three parameters of choice and Hedge's g was the summary effect size. The composite of HF hospitalization and all-cause death represented our clinical endpoint. Meta-regressions according to follow-up time were performed in order to explore potential heterogeneity sources across studies.
Results
We identified 9 prospective observational studies, enrolling 797 patients with HFpEF. On pooled analysis, patients with CMD present a more severe echocardiographic phenotype, determined by a higher LAVi effect size (ES) 0.40; Confidence Interval (CI) 0.11, 1.69, E/e’ ratio (ES 0.65; CI 0.28, 1.02) and LVMi (ES 0.27; CI 0.01, 0.53) compared to no-CMD patients. Furthermore, CMD patients showed a significant higher rate of the composite endpoint of all-cause-death and hospitalization for HF (HR 3.22, CI 1.2-8.5, p 0.02). At meta-regression, a significant correlation was found between logarithmic hazard ratios and follow-up time reported (z=2.03, p value 0.04), suggesting that long-term follow-up of CMD-HFpEF patients is required to track the natural trajectory of the disease.
Conclusions
Aside from being considered a pathophysiological hallmark in the development of HFpEF, CMD seems to play an aggravating role in the progression of the disease, leading both to more severe echocardiographic parameters and worse clinical outcomes compared to other endotypes. Thus, different echocardiographic thresholds could allow for a better prognostic stratification and for identifying the subset of patients who deserve a CMD assessment and who are eventually more likely to benefit from drugs targeting CMD.
Abstract
Background
Current guidelines recommend that patients with heart failure and a reduced ejection fraction (HFrEF) should receive four foundational treatments, i.e. renin-angiotensin system ...inhibitor (RASi) or angiotensin-receptor neprilysin inhibitor (ARNi), β-blocker, mineralocorticoid receptor antagonist (MRA) and sodium-glucose cotransporter 2 inhibitor (SGLT2i). There is emerging consensus that simultaneous initiation or rapid sequencing provide greater benefit, enhancing tolerability of these therapies and improving outcomes. However, implementation of a comprehensive approach is limited by common underuse and underdosing, and paucity of data exists on initiating the four pharmacological pillars of HFrEF during hospitalization or at discharge.
Aim
To investigate the feasibility of a comprehensive pharmacological approach in patients with HFrEF at discharge after an episode of heart failure (HF) hospitalization in a tertiary referral center.
Methods
In-patients with HFrEF and a first HF hospitalization (2019-2021) were categorized according to the number/type of treatments prescribed at discharge. Prevalence of contraindications and cautions for HFrEF treatments – as defined by current European Society of Cardiology (ESC) guidelines on HF – was as assessed. Logistic regression models were fitted to assess predictors of number of treatments prescribed and risk of re-hospitalization.
Results
Among 305 patients with HFrEF, 49.2% received at least two current recommended drugs. A β-blocker was prescribed in 93.4% of patients, and a RASi/ARNi in 68.2%. Based on current recommendations, 46.2% of patients could receive four foundational drugs. An MRA was prescribed in 32.5% of patients and 100% of patients did not show contraindications to MRA use. Renal dysfunction was present in 13.1% of patients, while hypotension in 11.8%. Bradycardia and renal dysfunction were associated with lower number of drugs prescribed adjusted OR (95% CI) 0.18 (0.06-0.50), and 0.50 (0.39-0.64), respectively. A higher number of drugs used was associated with no rehospitalization during the 30 days after discharge OR (95% CI) 0.22 (0.10-0.49) per number of pillars increase.
Conclusions
Based on the presence/absence of contraindications, a quadruple therapy could be implementable in a contemporary cohort of HFrEF in-patients at discharge. Renal dysfunction and bradycardia were the main prevalent conditions limiting the achievement of a more comprehensive therapeutic approach. Use of a higher number of drugs was associated with lower risk of re-hospitalization within 30 days after discharge.
Purpose of Review
The aim of this report is to describe the main aspects of sex-related differences in non-ischemic dilated cardiomyopathies (DCM), focusing on chemotherapy-induced heart failure (HF) ...and investigating the possible therapeutic implications and clinical management applications in the era of personalized medicine.
Recent Findings
In cardio-oncology, molecular and multimodality imaging studies confirm that sex differences do exist, affecting the therapeutic cardioprotective strategies and, therefore, the long-term outcomes. Interestingly, compelling evidences suggest that sex-specific characteristics in drug toxicity might predict differences in the therapeutic response, most likely due to the tangled interplay between cancer and HF, which probably share common underlying mechanisms.
Summary
Cardiovascular diseases show many sex-related differences in prevalence, etiology, phenotype expression, and outcomes. Complex molecular mechanisms underlie this diverse pathological manifestations, from sex-determined differential gene expression to sex hormone interaction with their receptors in the heart. Non-ischemic DCM is an umbrella definition that incorporates several etiologies, including chemotherapy-induced cardiomyopathies. The role of sex as a risk factor for cardiotoxicity is poorly explored. However, understanding the various features of disease manifestation and outcomes is of paramount importance for a prompt and tailored evaluation.
Abstract
Takotsubo syndrome (TTS) is a rare cardiac disease, characterized by transient regional wall motion abnormalities without evidence of obstructive coronary artery stenoses, mainly triggered ...by emotion or physical stressors. Reverse Takotsubo syndrome (rTTS), an atypical variant with basal segments involvement, is frequently associated with neurological disorders, including patients with amyotrophic lateral sclerosis (ALS). We reported the case of a 54 years old woman who experienced two consecutive episodes of TTS with different wall motion patterns, complicated by a recurrent episode and arrhythmic events.
A Caucasian woman, affected by ALS, was hospitalized in our department due to anemia and recurrent episodes of hematochezia. Following a week of relative clinical stability, the patient experienced acute deterioration with generalized malaise and worsening dyspnea. CT scan excluded pulmonary causes, whereas EKG (ST segment depression in the lower and lateral leads), blood test (increase in high-sensitive cardiac troponins) and TTE (severe impairment of LVEF, with akinesia of basal segments) revealed a cardiac etiology. Coronary angiography and left ventriculography were performed, documenting a wall motion pattern consistent with rTTS. After an initial management in intensive care unit, clinical stability was obtained with a complete recovery of left ventricular systolic function. The patient was discharged but one month later, due to bacterial pneumonia, she was readmitted in our ward and antibiotic therapy was started. Two days later an acute deterioration of clinical status occurred, characterized by dyspnea, altered state of consciousness and marked hypotension. TTE revealed a severe left ventricular systolic dysfunction with apical akinesia and preserved contractility of basal segments, so a diagnosis of typical TTS was made. Three weeks later the clinical scenario became more complicated due to advanced atrioventricular block, with phases of atrioventricular dissociation and ventricular escape-rhythm. Therefore, in light of the increased risk of infectious complications, she underwent implantation of a leadless pacemaker (PMK).
This clinical case represents the first report of recurrent episodes of TTS, one of which as rTTS, in a patient affected by ALS. It is worth noting that the first episode of TTS had atypical clinical presentation (dyspnea without chest pain), the EKG showed diffuse ST-segment depression (totally different from classical TTS typical electrocardiographic alterations), and TTE confirmed a different phenotype of segment involvement (unsurprisingly InterTAK Diagnostic Score was low). TTS recurrence is an extremely rare event, even if in this case there were two well defined triggers such as anemia and pneumonia. On the other hand it is reasonable to think that non-use of BBs after the first episode may have contributed to the occurrence of the next event, affecting different segments compared to the previous episode. Furthermore, advanced atrioventricular (AV) block represents a rare complication of TTS, most probably due to catecholamine stress or increased vagal tone, often requiring PMK implantation. In conclusion TTS represents an important frequent cardiac complication in patients affected by ALS, often still underdiagnosed. Therefore clinicians must keep their guard up with TTS, especially in the cases with atypical clinical presentation.
Abstract
Background
It is unclear which diagnostic strategy for detecting coronary artery disease (CAD) yields better outcomes. We aimed to compare the clinical accuracy and efficacy of non-invasive ...and invasive diagnostic strategies for the initial assessment of patients with suspected stable CAD.
Methods
On March 16, 2022, we searched PubMed, Embase, and CENTRAL databases for randomised controlled trials comparing diagnostic strategies for CAD detection among patients with symptoms suggestive of stable CAD. Diagnostic modalities included coronary computed tomographic angiography (CCTA), cardiovascular magnetic resonance (CMR), exercise electrocardiography, invasive coronary angiography (ICA), single photon emission computed tomography-myocardial perfusion imaging (SPECT-MPI), and stress echocardiography. Functional tests were grouped into a single node for the primary analyses, while being analysed as separate nodes for the secondary analyses. Frequentist random-effect network meta-analyses were conducted to summarise the evidence. GRADE frameworks were applied to rate the certainty of findings. The primary efficacy outcome was trial-defined major adverse cardiovascular events (MACE) and the primary accuracy outcome was the rate of unnecessary angiography. The study was registered with PROSPERO (CRD42022329635).
Results
Twenty trials (n=27753 participants) were included. Compared with direct-ICA referral, CCTA and functional testing provided no significant difference in the risk of MACE (incidence rate ratios IRRs 0·87 95% CI 0·65-1·17 and 1·19 95% CI 0·87-1·62, respectively; moderate certainty) and a large reduction in the rate of unnecessary angiography (odds ratios 0·04 95% CI 0·02-0·09 and 0·08 95% CI 0·03-0·18, respectively; high certainty). Among non-invasive diagnostic strategies, CCTA significantly reduced the risk of MACE compared with functional testing (IRR 0·73, 95% CI 0·57-0·95; high certainty). The worse prognostic performance of functional testing was mainly driven by the poor efficacy of exercise electrocardiography (high certainty) and stress echocardiography (moderate to low certainty), whose risk of MACE was significantly reduced by CCTA (IRRs 0·56 95% CI 0·42-0·75 and 0·59 95% CI 0·42-0·81, respectively), SPECT-MPI (IRRs 0·56 95% CI 0·41-0·77 and 0·59 95% CI 0·43-0·81, respectively), and direct-ICA referral (IRRs 0·64 95% CI 0·45-0·91 and 0·67 95% CI 0·48-0·92, respectively), while non-significantly reduced by CMR (IRRs 0·71 95% CI 0·47-1·06 and 0·74 95% CI 0·53-1·04, respectively).
Conclusion
In patients with suspected stable CAD, an initial assessment with non-invasive diagnostic strategies is safe and addresses the low diagnostic yield of direct-ICA referral. CCTA is among the most effective strategies in terms of both clinical accuracy and efficacy. Among functional non-invasive tests, exercise electrocardiography and stress echocardiography may not be deemed effective diagnostic alternatives, while SPECT-MPI and CMR are valuable and feasible options, respectively.
Extensive data support the safety of direct oral anticoagulants compared with vitamin K antagonists in patients with non‐valvular atrial fibrillation, leading to a significantly increase in the use ...of these compounds in clinical practice. However, there is no compelling evidence supporting the use of direct oral anticoagulant in individuals who are intubated or have a percutaneous endoscopic gastrostomy (PEG): patients with several co‐morbidities are underrepresented in clinical trials, so the best long‐term strategy for anticoagulation is difficult to ascertain. The aim of the present report was to evaluate the safety and efficacy of edoxaban administered via PEG in a patient with heart failure and a history of atrial fibrillation affected by amyotrophic lateral sclerosis (ALS). A 71‐year‐old man with atrial fibrillation, advanced ALS, type II diabetes mellitus, and hypertension presented to the emergency department with dyspnoea and tachycardia. Because vitamin K antagonist and rivaroxaban 15 mg were dropped because of difficult international normalized ratio control (time in therapeutic range <30%) and severe haematuria, respectively, edoxaban 30 mg (crushed pill) daily was administered based on the patient's weight of 58 kg. Mean edoxaban plasma concentration–time profiles were measured, as anti‐Xa activity, 2 h before and at 2, 6, and 22 h after drug administration and then compared with the pharmacokinetic profile of edoxaban 30 mg in healthy subjects. An additional testing of steady‐state peak plasma concentration of edoxaban after 10 days and a 30 day follow‐up were evaluated. The values of the pharmacokinetic parameters, analysed with a non‐compartmental analysis by PKSolver module, showed that Cmax and AUC0→t were only slightly higher than those observed in healthy subjects, while the half‐life and observed clearance were significantly longer and lower, respectively, than in normal subjects. Steady‐state peak plasma concentration of edoxaban was very similar to the levels reported in healthy subjects, and neither relevant bleeding nor thromboembolic event was reported at a 30 day follow‐up. These results support safe and effective anticoagulation with edoxaban 30 mg but suggest caution with the use of full dose of edoxaban (60 mg daily) in this kind of patients. We report, for the first time, a safe and effective anticoagulation based on the administration of edoxaban 30 mg daily through PEG in a patient with advanced ALS, acute respiratory, and heart failure, presenting with Takotsubo syndrome and atrial fibrillation.
Abstract
Introduction
Atherosclerotic plaque healing is a dynamic process that promotes plaque repair after destabilization. Previous studies showed that healed plaques are more common in patients ...with chronic coronary syndrome than in those with acute coronary syndrome, suggesting that they might be a marker of clinical stability. The mechanisms underlying plaque healing are not completely understood. The aim of the present study was to evaluate sex-based differences in plaque phenotype and healing of non-culprit coronary lesions by optical coherence tomography.
Methods
In this observational, single-center cohort study, we enrolled patients from the OCT Registry of the Fondazione Policlinico A Gemelli IRCCS. A total of 205 patients with both acute coronary syndromes or chronic coronary syndromes undergoing coronary angiography and intravascular OCT imaging of non-culprit vessels were included in the analysis and divided into two groups according to gender.
Results
Of 205 patients, 153 were male (75%) and 52 (25%) female. Compared with male patients, female patients had lower prevalence of lipid-rich plaque (40.4% vs. 57.7%; p=0.030), plaque rupture (7.7% vs. 21.2%; p=0.028) and cholesterol crystal (13.5% vs. 29.5%; p=0.022). Mean lipid arc and calcium depht were significantly lower in female patients than in male ones (118.0° ± 79.9° vs. 135.5° ± 77.9°; p=0.011; and 52.7 µm ± 79.2 µm vs. 72.3 µm ± 93.5 µm; p=0.007) while fibrous cap tended to be thicker (108.2 µm ± 70.4 µm vs. 96.2 µm ± 72.9 µm; p=0.055). Healed plaques were significantly more frequent in female patients than in male patients (51.9% vs 34.6%; p = 0.027). The prevalence of fibrous plaque, thrombi, neovascularization, diffuse calcifications and spotty calcification was not different between the two groups.
Conclusion
Females have a distinct atherosclerotic phenotype and healing capacity compared with male patients, including lower prevalence of lipid-rich plaque, cholesterol crystals and plaque ruptures and higher prevalence of healed plaques in non-culprit coronary lesions.
Abstract
Background
Percutaneous coronary intervention (PCI) is the milestone of treatment for patients with acute coronary syndrome (ACS). However, a considerable number of patients do not achieve a ...complete myocardial reperfusion since coronary microvascular obstruction (CMVO) might occur. Adenosine is one of the pharmacological strategies tested in several randomized controlled trials (RCTs) to minimize the incidence of CMVO. However, conflicting results have been reported so far. The aim of the present study was to evaluate all the RCTs comparing intracoronary or intravenous adenosine versus placebo as adjunctive therapy in patients with ACS undergoing PCI or thrombolysis.
Methods
PubMed and Scopus electronic databases were scanned for eligible studies up to June 5th, 2022. Our meta-analysis included 26 randomized RCTs with a total of 5843 patients involved. Primary endpoints were the rate of clinical events, defined as major adverse cardiovascular events (MACE), heart failure (HF), all-cause-death and non-fatal myocardial infarction (MI). The rate of advanced atrioventricular (AV) blocks and ventricular fibrillation/sustained ventricular tachycardia (VF/SVT) were considered as safety endpoints. Further subgroup analyses and meta regressions were conducted to evaluate the role of different procedural and non-procedural factors influencing the results. Finally, a secondary analysis was conducted only including RCTs enrolling patients with ST-segment elevation myocardial infarction (STEMI).
Results
Adenosine administration did not confer any significant clinical benefit in terms of reduction of MACE (RR 0.91 CI 0.79-1.05, p 0.16), all-cause-death (RR 0.90 CI0.74-1.09, p 0.28), non-fatal MI (RR 1 CI 0.74 - 1.35, p 0.44) and HF (RR 0.94 CI 0.77-1.16, p 0.59). Remarkably, adenosine was associated with a significant reduction of post-procedural CMVO parameters such as Myocardial Blush Grade (MBG) 0-1 (RR 0.69 CI 0.53-0.90, p 0.01) and Thrombolysis In Myocardial Infarction (TIMI) flow grade 0-2 (RR 0.67 CI 0.53-0.85, p <0.01), when compared to placebo. Secondary analyses of STEMI patients showed similar results. As regards safety, adenosine therapy was associated with a higher rate of advanced AV blocks (RR 2.72 CI 1.57-4.74, p <0.01). A higher rate of VF/SVT was observed with adenosine in studies with total mean ischemic time >3 hours (RR 1.67 CI 1.14-2.42)
Conclusions
This is the most up-to-date meta-analysis summarizing the available evidence on adenosine safety and efficacy in the prevention or treatment of CMVO in ACS patients. Although adenosine improves surrogate parameters of myocardial perfusion, its use does not provide any clinical benefits. Additionally, adenosine infusion increases the risk of advanced AV blocks. Moreover, a longer ischemic time seems to be associated with a higher rate of adenosine-triggered ventricular arrhythmias, suggesting that higher myocardial ischemic damage may represent a substrate for adenosine arrhythmogenic effects.
Abstract
Introduction
Pathological studies have shown that many atherosclerotic plaques destabilize without resulting in a clinical manifestation. Recent in vivo studies showed that healed plaques ...are more common in patients with chronic coronary syndrome (CCS) than in those with acute coronary syndrome (ACS), suggesting that they might be a marker of clinical stability. The aim of the present study was to evaluate the clinical impact of healed coronary plaques detected by optical coherence tomography (OCT) imaging.
Methods
A total of 208 patients with CCS or ACS who underwent OCT imaging of non-target/non-culprit vessels were enrolled. Only non-culprit segments were analyzed. Patients were divided into two groups according to the presence or absence of healed plaques detected by OCT. The incidence of major adverse cardiac events (MACE) at follow-up was assessed, defined as the composite of cardiac death, non-fatal myocardial infarction, and target vessel revascularization (TVR).
Results
Healed coronary plaques were observed in 39.7% of patients, and the prevalence was higher in those presenting with chronic coronary syndrome. Median follow-up time was 4 years, and was not different between the two groups. Patients with healed plaques had a significantly lower incidence of MACE at follow-up (13.6% vs 22%, p=0.019), mainly driven by a lower rate of non-fatal myocardial infarctions (4.9% vs 10.2%, p=0.05). The incidence of cardiac death and TVR was not significantly different between the two groups (1.2% vs. 3.1%, p=0.288; and 13.6% vs. 15.0%, p= 0.187, respectively). At multivariate Cox regression analysis, the presence of plaque disruption was an independent predictor of MACE (odds ratio OR 3.33, 95% confidence interval CI 1.39-7.98, p=0.007), while the presence of healed plaque was an independent protective factor (OR 0.44, 95% CI 0.22-0.89, p=0.022).
Conclusions
Healed coronary plaques detected by OCT imaging are associated with a favorable clinical outcome at long-term follow-up.
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