Diagnostic Strategies for the Assessment of Suspected Stable Coronary Artery Disease : A Systematic Review and Meta-analysis.

BACKGROUND: There is uncertainty about which diagnostic strategy for detecting coronary artery disease (CAD) provides better outcomes. PURPOSE: To compare the effect on clinical management and subsequent health effects of alternative diagnostic strategies for the initial assessment of suspected stable CAD. DATA SOURCES: PubMed, Embase, and Cochrane Central Register of Controlled Trials. STUDY SELECTION: Randomized clinical trials comparing diagnostic strategies for CAD detection among patients with symptoms suggestive of stable CAD. DATA EXTRACTION: Three investigators independently extracted study data. DATA SYNTHESIS: The strongest available evidence was for 3 of the 6 comparisons: coronary computed tomography angiography (CCTA) versus invasive coronary angiography (ICA) (4 trials), CCTA versus exercise electrocardiography (ECG) (2 trials), and CCTA versus stress single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) (5 trials). Compared with direct ICA referral, CCTA was associated with no difference in cardiovascular death and myocardial infarction (relative risk [RR], 0.84 [95% CI, 0.52 to 1.35]; low certainty) but less index ICA (RR, 0.23 [CI, 0.22 to 0.25]; high certainty) and index revascularization (RR, 0.71 [CI, 0.63 to 0.80]; moderate certainty). Moreover, CCTA was associated with a reduction in cardiovascular death and myocardial infarction compared with exercise ECG (RR, 0.66 [CI, 0.44 to 0.99]; moderate certainty) and SPECT-MPI (RR, 0.64 [CI, 0.45 to 0.90]; high certainty). However, CCTA was associated with more index revascularization (RR, 1.78 [CI, 1.33 to 2.38]; moderate certainty) but less downstream testing (RR, 0.56 [CI, 0.45 to 0.71]; very low certainty) than exercise ECG. Low-certainty evidence compared SPECT-MPI versus exercise ECG (2 trials), SPECT-MPI versus stress cardiovascular magnetic resonance imaging (1 trial), and stress echocardiography versus exercise ECG (1 trial). LIMITATION: Most comparisons primarily rely on a single study, many studies were underpowered to detect potential differences in direct health outcomes, and individual patient data were lacking. CONCLUSION: For the initial assessment of patients with suspected stable CAD, CCTA was associated with similar health effects to direct ICA referral, and with a health benefit compared with exercise ECG and SPECT-MPI. Further research is needed to better assess the relative performance of each diagnostic strategy. PRIMARY FUNDING SOURCE: None. (PROSPERO: CRD42022329635).

Dapagliflozin treatment is associated with a reduction of epicardial adipose tissue thickness and epicardial glucose uptake in human type 2 diabetes.

OBJECTIVE: We recently demonstrated that treatment with sodium-glucose cotransporter-2 inhibitors (SGLT-2i) leads to an increase in myocardial flow reserve in patients with type 2 diabetes (T2D) with stable coronary artery disease (CAD). The mechanism by which this occurs is, however, unclear. One of the risk factors for cardiovascular disease is inflammation of epicardial adipose tissue (EAT). Since the latter is often increased in type 2 diabetes patients, it could play a role in coronary microvascular dysfunction. It is also well known that SGLT-2i modify adipose tissue metabolism. We aimed to investigate the effects of the SGLT-2i dapagliflozin on metabolism and visceral and subcutaneous adipose tissue thickness in T2D patients with stable coronary artery disease and to verify whether these changes could explain observed changes in myocardial flow. METHODS: We performed a single-center, prospective, randomized, double-blind, controlled clinical trial with 14 T2D patients randomized 1:1 to SGLT-2i dapagliflozin (10 mg daily) or placebo. The thickness of visceral (epicardial, mediastinal, perirenal) and subcutaneous adipose tissue and glucose uptake were assessed at baseline and 4 weeks after treatment initiation by 2-deoxy-2-[18F]fluoro-D-glucose Positron Emission Tomography/Computed Tomography during hyperinsulinemic euglycemic clamp. RESULTS: The two groups were well-matched for baseline characteristics (age, diabetes duration, HbA1c, BMI, renal and heart function). Dapagliflozin treatment significantly reduced EAT thickness by 19% (p = 0.03). There was a significant 21.6% reduction in EAT glucose uptake during euglycemic hyperinsulinemic clamp in the dapagliflozin group compared with the placebo group (p = 0.014). There were no significant effects on adipose tissue thickness/metabolism in the other depots explored. CONCLUSIONS: SGLT-2 inhibition selectively reduces EAT thickness and EAT glucose uptake in T2D patients, suggesting a reduction of EAT inflammation. This could explain the observed increase in myocardial flow reserve, providing new insights into SGLT-2i cardiovascular benefits.

Guided versus standard antiplatelet therapy in patients undergoing percutaneous coronary intervention: a systematic review and meta-analysis.

BACKGROUND: Whether guided selection of antiplatelet therapy in patients undergoing percutaneous coronary intervention (PCI) is effective in improving outcomes compared with standard antiplatelet therapy remains controversial. We assessed the safety and efficacy of guided versus standard selection of antiplatelet therapy in patients undergoing PCI. METHODS: For this systematic review and meta-analysis, from Aug 20 to Oct 25, 2020, we searched MEDLINE (via PubMed), Cochrane, Embase, and Web of Science databases for randomised controlled trials and observational studies published in any language that compared guided antiplatelet therapy, by means of platelet function testing or genetic testing, versus standard antiplatelet therapy in patients undergoing PCI. Two reviewers independently assessed study eligibility, extracted the data, and assessed risk of bias. Risk ratios (RRs) and 95% CIs were used with random-effects or fixed-effect models according to the estimated heterogeneity among studies assessed by the I2 index. Coprimary endpoints were trial-defined primary major adverse cardiovascular events and any bleeding. Key secondary endpoints were all-cause death, cardiovascular death, myocardial infarction, stroke, definite or probable stent thrombosis, and major and minor bleeding. This study is registered with PROSPERO (CRD42021215901). FINDINGS: 3656 potentially relevant articles were screened. Our analysis included 11 randomised controlled trials and three observational studies with data for 20 743 patients. Compared with standard therapy, guided selection of antiplatelet therapy was associated with a reduction in major adverse cardiovascular events (RR 0·78, 95% CI 0·63-0·95, p=0·015) and reduced bleeding, although not statistically significant (RR 0·88, 0·77-1·01, p=0·069). Cardiovascular death (RR 0·77, 95% CI 0·59-1·00, p=0·049), myocardial infarction (RR 0·76, 0·60-0·96, p=0·021), stent thrombosis (RR 0·64, 0·46-0·89, p=0·011), stroke (RR 0·66, 0·48-0·91, p=0·010), and minor bleeding (RR 0·78, 0·67-0·92, p=0·0030) were reduced with guided therapy compared with standard therapy. Risks of all-cause death and major bleeding did not differ between guided and standard approaches. Outcomes varied according to the strategy used, with an escalation approach associated with a significant reduction in ischaemic events without any trade-off in safety, and a de-escalation approach associated with a significant reduction in bleeding, without any trade-off in efficacy. INTERPRETATION: Guided selection of antiplatelet therapy improved both composite and individual efficacy outcomes with a favourable safety profile, driven by a reduction in minor bleeding, supporting the use of platelet function or genetic testing to optimise the choice of agent in patients undergoing PCI. FUNDING: None.

The V-LAP System for Remote Left Atrial Pressure Monitoring of Patients With Heart Failure: Remote Left Atrial Pressure Monitoring.

OBJECTIVE: Patients with heart failure (HF) are at an increased risk of hospital admissions. The aim of this report is to describe the feasibility, safety and accuracy of a novel wireless left atrial pressure (LAP) monitoring system in patients with HF. METHODS: The V-LAP Left Atrium Monitoring systEm for Patients With Chronic sysTOlic & Diastolic Congestive heart Failure (VECTOR-HF) study is a prospective, multicenter, single-arm, open-label, first-in human clinical trial to assess the safety, performance and usability of the V-LAP system (Vectorious Medical Technologies) in patients with New York Heart Association class III HF. The device was implanted in the interatrial septum via a percutaneous, trans-septal approach guided by fluoroscopy and echocardiography. Primary endpoints included the successful deployment of the implant, the ability to perform initial pressure measurements and safety outcomes. RESULTS: To date, 24 patients have received implants of the LAP-monitoring device. No device-related complications have occurred. LAP was reported accurately, agreeing well with wedge pressure at 3 months (Lin concordance correlation coefficient = 0.850). After 6 months, New York Heart Association class improved in 40% of the patients (95% CI = 16.4%-63.5%), while the 6-minute walk test distance had not changed significantly (313.9 ± 144.9 vs 232.5 ± 129.9 meters; P = 0.076). CONCLUSION: The V-LAP left atrium monitoring system appears to be safe and accurate.

Dapagliflozin improves myocardial flow reserve in patients with type 2 diabetes: the DAPAHEART Trial: a preliminary report.

OBJECTIVE: Cardiovascular (CV) outcome trials have shown that in patients with type 2 diabetes (T2D), treatment with sodium-glucose cotransporter-2 inhibitors (SGLT-2i) reduces CV mortality and hospital admission rates for heart failure (HF). However, the mechanisms behind these benefits are not fully understood. This study was performed to investigate the effects of the SGLT-2i dapagliflozin on myocardial perfusion and glucose metabolism in patients with T2D and stable coronary artery disease (coronary stenosis ≥ 30% and < 80%), with or without previous percutaneous coronary intervention (> 6 months) but no HF. METHODS: This was a single-center, prospective, randomized, double-blind, controlled clinical trial including 16 patients with T2D randomized to SGLT-2i dapagliflozin (10 mg daily) or placebo. The primary outcome was to detect changes in myocardial glucose uptake (MGU) from baseline to 4 weeks after treatment initiation by [(18)F]2-deoxy-2-fluoro-D-glucose (FDG) PET/CT during hyperinsulinemic euglycemic clamp. The main secondary outcome was to assess whether the hypothetical changes in MGU were associated with changes in myocardial blood flow (MBF) and myocardial flow reserve (MFR) measured by 13N-ammonia PET/CT. The study was registered at eudract.ema.europa.eu (EudraCT No. 2016-003614-27) and ClinicalTrials.gov (NCT03313752). RESULTS: 16 patients were randomized to dapagliflozin (n = 8) or placebo (n = 8). The groups were well-matched for baseline characteristics (age, diabetes duration, HbA1c, renal and heart function). There was no significant change in MGU during euglycemic hyperinsulinemic clamp in the dapagliflozin group (2.22 ± 0.59 vs 1.92 ± 0.42 µmol/100 g/min, p = 0.41) compared with the placebo group (2.00 ± 0.55 vs 1.60 ± 0.45 µmol/100 g/min, p = 0.5). Dapagliflozin significantly improved MFR (2.56 ± 0.26 vs 3.59 ± 0.35 p = 0.006 compared with the placebo group 2.34 ± 0.21 vs 2.38 ± 0.24 p = 0.81; pint = 0.001) associated with a reduction in resting MBF corrected for cardiac workload (p = 0.005; pint = 0.045). A trend toward an increase in stress MBF was also detected (p = 0.054). CONCLUSIONS: SGLT-2 inhibition increases MFR in T2D patients. We provide new insight into SGLT-2i CV benefits, as our data show that patients on SGLT-2i are more resistant to the detrimental effects of obstructive coronary atherosclerosis due to increased MFR, probably caused by an improvement in coronary microvascular dysfunction. Trial registration EudraCT No. 2016-003614-27; ClinicalTrials.gov Identifier: NCT03313752.

Instantaneous wave-free ratio-guided revascularization of nonculprit lesions in STEMI patients with multivessel coronary disease: The WAVE registry.

BACKGROUND: Complete revascularization (CR) of nonculprit lesions (NCL) is strongly recommended in patients with ST-elevation myocardial infarction (STEMI) and multivessel coronary artery disease (MVD), but no definitive evidence is available regarding which diagnostic strategy should be preferred. Instantaneous wave-free ratio (iFR) has never been investigated in this setting. We aimed to describe clinical outcomes of a cohort of patients undergoing iFR-guided CR. METHODS: Following primary percutaneous coronary intervention (PCI), consecutive patients with STEMI and intermediate NCL were enrolled and destinated to an iFR-guided CR. NCL with iFR ≤ 0.89 underwent PCI while NCL with iFR > 0.89 were deferred. The primary endpoint was NC target lesion failure (NC-TLF) and the secondary endpoint was major adverse cardiovascular events (MACE), at 1-year follow-up. RESULTS: Overall, 209 patients were enrolled (ischemic iFR = 83; nonischemic iFR = 126). Patients with ischemic iFR showed a higher prevalence of traditional cardiovascular risk factors and angiographically determined three-vessel disease. In the entire cohort, NC-TLF and MACE occurred in 6.7% and 10.5% of patients, respectively. Compared to the deferred group, patients with ischemic iFR experienced significantly higher rates of both NC-TLF (3.2% vs. 12.1%; p = 0.021) and MACE (7.1% vs. 16.9%; p = 0.041). These results were mostly driven by increased rates of NC-TLF PCI and further revascularizations in this latter group, while no differences were evident in terms of nonfatal myocardial infarction or death. At multivariable analysis, the strongest predictor of MACE was symptom onset to balloon time (HR = 1.17 [95% CI: 1.04-1.31], p = 0.008). CONCLUSIONS: In our study enrolling STEMI patients with MVD, iFR assessment was feasible and safe. PCI-deferring according to iFR evaluation of NCL was associated with low rates of adverse events. Further randomized studies are needed to investigate the effectiveness of iFR-guided revascularization compared to current practice in this setting.

Long-term clinical impact of permanent pacemaker implantation in patients undergoing transcatheter aortic valve implantation: a systematic review and meta-analysis.

AIMS: The aims of this study is to assess by an updated meta-analysis the clinical outcomes related to permanent pacemaker implantation (PPI) after transcatheter aortic valve implantation (TAVI) at long-term (≥12 months) follow-up (LTF). METHODS AND RESULTS: A comprehensive literature research was performed on PubMed and EMBASE. The primary endpoint was all-cause death. Secondary endpoints were rehospitalization for heart failure, stroke, and myocardial infarction. A subgroup analysis was performed according to the Society of Thoracic Surgeon-Predicted Risk of Mortality (STS-PROM) score. This study is registered with PROSPERO (CRD42021243301). A total of 51 069 patients undergoing TAVI from 31 observational studies were included. The mean duration of follow-up was 22 months. At LTF, PPI post-TAVI was associated with a higher risk of all-cause death [risk ratio (RR) 1.18, 95% confidence interval (CI) 1.10-1.25; P < 0.001] and rehospitalization for heart failure (RR 1.32, 95% CI 1.13-1.52; P < 0.001). In contrast, the risks of stroke and myocardial infarction were not affected. Among the 20 studies that reported procedural risk, the association between PPI and all-cause death risk at LTF was statistically significant only in studies enrolling patients with high STS-PROM score (RR 1.25, 95% CI 1.12-1.40), although there was a similar tendency of the results in those at medium and low risk. CONCLUSION: Patients necessitating PPI after TAVI have a higher long-term risk of all-cause death and rehospitalization for heart failure as compared to those who do not receive PPI.

Efficacy of high-dose atorvastatin or rosuvastatin loading in patients with acute coronary syndrome undergoing percutaneous coronary intervention: a meta-analysis of randomized controlled trials with GRADE qualification of available evidence.

PURPOSE: We aimed to summarize current evidence regarding the impact of a high-dose statin loading before percutaneous coronary intervention (PCI) on short-term outcomes in patients presenting with the acute coronary syndrome (ACS). METHODS: This meta-analysis was based on a search of the MEDLINE, Cochrane Central Register of Controlled Trials, Ovid Journals, and SCOPUS for randomized controlled trials that compared high-dose atorvastatin or rosuvastatin with no or low-dose statin administered before planned PCI in statin-naive patients with ACS. The primary endpoints were major adverse cardiovascular and cerebrovascular events (MACCE), myocardial infarction (MI), and all-cause mortality at 30 days. Prespecified subanalyses were performed with respect to statin and ACS type. RESULTS: A total of eleven trials enrolling 6291 patients were included, of which 75.4% received PCI. High-dose statin loading was associated with an overall 43% relative risk (RR) reduction in MACCE at 30 days (RR 0.57, 95% CI 0.41-0.77) in whole ACS population. This effect was primarily driven by the 39% reduction in the occurrence of MI (RR 0.61, 95% CI 0.46-0.80). No significant effect on all-cause mortality reduction was observed (RR 0.92, 95% CI 0.67-1.26). In the setting of ST-elevation myocardial infarction (STEMI), atorvastatin loading was associated with a 33% reduction in MACCE (RR 0.67, 95% CI 0.48-0.94), while in non-ST-elevation myocardial infarction ACS (NSTE-ACS), rosuvastatin loading was associated with 52% reduction in MACCE at 30 days (RR 0.48, 95% CI 0.34-0.66). The level of evidence as qualified with GRADE was low to high, depending on the outcome. CONCLUSION: A high-dose loading of statins before PCI in patients with ACS reduces MACCE and reduces the risk of MI with no impact on mortality at 30 days. Atorvastatin reduces MACCE in STEMI while rosuvastatin reduces MACCE in NSTE-ACS at 30 days.

Impact of progressive aortic regurgitation on outcomes after left ventricular assist device implantation.

Aortic regurgitation (AR) following continuous flow left ventricular assist device implantation (cf-LVAD) may adversely impact outcomes. We aimed to assess the incidence and impact of progressive AR after cf-LVAD on prognosis, biomarkers, functional capacity and echocardiographic findings. In an analysis of the PCHF-VAD database encompassing 12 European heart failure centers, patients were dichotomized according to the progression of AR following LVAD implantation. Patients with de-novo AR or AR progression (AR_1) were compared to patients without worsening AR (AR_0). Among 396 patients (mean age 53 ± 12 years, 82% male), 153 (39%) experienced progression of AR over a median of 1.4 years on LVAD support. Before LVAD implantation, AR_1 patients were less frequently diabetic, had lower body mass indices and higher baseline NT-proBNP values. Progressive AR did not adversely impact mortality (26% in both groups, HR 0.91 [95% CI 0.61-1.36]; P = 0.65). No intergroup variability was observed in NT-proBNP values and 6-minute walk test results at index hospitalization discharge and at 6-month follow-up. However, AR_1 patients were more likely to remain in NYHA class III and had worse right ventricular function at 6-month follow-up. Lack of aortic valve opening was related to de-novo or worsening AR (P < 0.001), irrespective of systolic blood pressure (P = 0.67). Patients commonly experience de-novo or worsening AR when exposed to continuous flow of contemporary LVADs. While reducing effective forward flow, worsening AR did not influence survival. However, less complete functional recovery and worse RV performance among AR_1 patients were observed. Lack of aortic valve opening was associated with progressive AR.

Myocardial bridge evaluation towards personalized medicine: study design and preliminary results of the RIALTO registry.

Myocardial bridge (MB) is the most frequent inborn coronary artery variant in which a portion of the myocardium overlies an epicardial coronary artery segment. Although MB has long been considered a benign entity, a growing body of evidence has suggested its association with angina and adverse cardiac events. However, to date, no data on long-term prognosis are available, nor on therapies improving cardiovascular outcomes. We are currently conducting an ambispective, observational, multicentre, study in which we enrol patients with a clinical indication to undergo coronary angiography (CA) and evidence of MB, aiming to describe the incidence of symptoms and cardiovascular events at baseline and at long-term follow-up (FUP). The role of invasive full-physiology assessment in modifying the discharge therapy and eventually the perceived quality of life and the incidence of major cardiovascular events will be analysed. Basal clinical-instrumental data of eligible and consenting patients have been acquired after CA; FUP was performed 6, 12, and 24 months after the angiographic diagnosis of MB. The primary endpoint of the study is the incidence of major adverse cardiovascular events (MACE), defined as the composite of cardiac death, myocardial infarction, cardiac hospitalization, and target vessel revascularization; the secondary endpoints are the rate of patients with Seattle Angina Questionnaire (SAQ) summary score <70 and the incidence of MACE in patients undergoing invasive intracoronary assessment. Among patients undergone FUP visits, we recorded 31 MACE at 6 months (11.6%), 16 MACE at 12 months (6.5%), and 26 MACE at 24 months (13.5%). The rate of patients with SAQ <70 is 18.8% at 6 months, 20.6% at 12 months, and 21.8% at 24 months. To evaluate the prognostic role of invasive intracoronary assessment, we compared MB patients who underwent only angiographic evaluation (Angio group) to those who underwent acetylcholine (ACH) provocative test with indication to calcium-channel blockers (CCBs) at discharge (Angio + ACH + CCBs group) and those who underwent functional assessment with fractional flow reserve (FFR) with indication to beta-blockers (BBs) at discharge (Angio + FFR + BBs group). After 2 years of FUP, the rate of MACE was significantly reduced in both Angio + ACH + CCBs group (6 vs. 25%, P = 0.029) and Angio + FFR + BBs group (3 vs. 25%, P = 0.005) compared with Angio group. The preliminary results of our study showed that MB may be a cause of angina and adverse cardiac events in patients referred to CA for suspected coronary artery disease (CAD). Full-physiology assessment unmasking MB-related ischaemia mechanisms, allowed to guide the treatment, personalizing the clinical management, improving the quality of life, and cardiovascular outcomes in patients with MB.

Cardiac contractility modulation for patient with refractory heart failure: an updated evidence-based review.

Heart failure is the cardiovascular epidemic of the twenty-first century, with poor prognosis and quality of life despite optimized medical treatment. Despite over the last decade significant improvements, with a major impact on morbidity and mortality, have been made in therapy for heart failure with reduced ejection fraction, little progress was made in the development of devices, with the implantable defibrillator indicated for patients with left ventricle ejection fraction ≤ 35% and cardiac resynchronization therapy for those with QRS ≥ 130 ms and evidence of left bundle branch block. Nevertheless, only a third of patients meet these criteria and a high percentage of patients are non-responders in terms of improving symptoms. Nowadays, in patients with symptomatic heart failure with ejection fraction between 25% and 45% and QRS < 130 ms, not eligible for cardiac resynchronization, the cardiac contractility modulation (CCM) represents a concrete therapeutic option, having proved to be safe and effective in reducing hospitalizations for heart failure and improving symptoms, functional capacity, and quality of life. The aim of this review is therefore to summarize the pathophysiological mechanisms, the current indications, and the recent developments regarding the new applications of the CCM for patients with chronic heart failure.

Amelioration of diastolic dysfunction by dapagliflozin in a non-diabetic model involves coronary endothelium.

The results of trials with sodium-glucose cotransporter 2 (SGLT2) inhibitors raised the possibility that this class of drugs provides cardiovascular benefits independently from their anti-diabetic effects, although the mechanisms are unknown. Therefore, we tested the effects of SGLT2 inhibitor dapagliflozin on the progression of experimental heart disease in a non-diabetic model of heart failure with preserved ejection fraction. Dahl salt-sensitive rats were fed a high-salt diet to induce hypertension and diastolic dysfunction and were then treated with dapagliflozin for six weeks. Dapagliflozin ameliorated diastolic function as documented by echo-Doppler and heart catheterization, while blood pressure remained markedly elevated. Chronic in vivo treatment with dapagliflozin reduced diastolic Ca2+ and Na+ overload and increased Ca2+ transient amplitude in ventricular cardiomyocytes, although no direct action of dapagliflozin on isolated cardiomyocytes was observed. Dapagliflozin reversed endothelial activation and endothelial nitric oxide synthase deficit, with reduced cardiac inflammation and consequent attenuation of pro-fibrotic signaling. The potential involvement of coronary endothelium was supported by the endothelial upregulation of Na+/H+ exchanger 1in vivo and direct effects on dapagliflozin on the activity of this exchanger in endothelial cells in vitro. In conclusions, several mechanisms may cumulatively play a significant role in the dapagliflozin-associated cardioprotection. Dapagliflozin ameliorates diastolic function and exerts a positive effect on the myocardium, possibly targeting coronary endothelium. The lower degree of endothelial dysfunction, inflammation and fibrosis translate into improved myocardial performance.

Sex-Related Differences in Dilated Cardiomyopathy with a Focus on Cardiac Dysfunction in Oncology.

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. 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.

Long-Term Outcomes of Extent of Revascularization in Complex High Risk and Indicated Patients Undergoing Impella-Protected Percutaneous Coronary Intervention: Report from the Roma-Verona Registry.

OBJECTIVE: To investigate the effect of extent of revascularization in complex high-risk indicated patients (CHIP) undergoing Impella-protected percutaneous coronary intervention (PCI). BACKGROUND: Complete revascularization has been shown to be associated with improved outcomes. However, the impact of more complete revascularization during Impella-protected PCI in CHIP has not been reported. METHODS: A total of 86 CHIP undergoing elective PCI with Impella 2.5 or Impella CP between April 2007 and December 2016 from 2 high volume Italian centers were included. Baseline, procedural, and clinical outcomes data were collected retrospectively. Completeness of coronary revascularization was assessed using the British Cardiovascular Intervention Society myocardial jeopardy score (BCIS-JS) derived revascularization index (RI). The primary end-point was all-cause mortality. A multivariate regression model was used to identify independent predictors of mortality. RESULTS: All patients had multivessel disease and were considered unsuitable for surgery. At baseline, 44% had left main disease, 78% had LVEF ≤ 35%, and mean BCIS-JS score was 10±2. The mean BCIS-JS derived RI was 0.7±0.2 and procedural complications were uncommon. At 14-month follow-up, all-cause mortality was 10.5%. At follow-up, 67.4% of CHIP had LVEF ≥ 35% compared to 22.1% before Impella protected-PCI. Higher BCIS-JS RI was significantly associated with LVEF improvement (p=0.002). BCIS-JS RI of ≤ 0.8 (HR 0.11, 95% CI 0.01- 0.92, and p = 0.042) was an independent predictor of mortality. CONCLUSIONS: These results support the practice of percutaneous Impella use for protected PCI in CHIP. A more complete revascularization was associated with significant LVEF improvement and survival.

Granulocyte colony-stimulating factor for the treatment of cardiovascular diseases: An update with a critical appraisal.

Heart failure and acute myocardial infarction are conditions that are associated with high morbidity and mortality. Significant dysfunction of the heart muscle can occur as the consequence of end-stage chronic cardiovascular diseases or acute ischemic events that are marked by large infarction area and significant tissue necrosis. Despite the remarkable improvement of conventional treatments, a substantial proportion of patients still develops severe heart failure that can only be resolved by heart transplantation or mechanical device implantation. Therefore, novel approaches based on stem-cell therapy can directly modify the disease process and alter its prognosis. The ability of the stem-cells to modify and repair the injured myocardium is a challenging but intriguing concept that can potentially replace expensive and invasive methods of treatment that are associated with increased risks and significant financial costs. In that sense, granulocyte colony-stimulating factor (G-CSF) seems as an attractive treatment approach. Based on the series of pre-clinical experiments and a limited amount of clinical data, it was demonstrated that G-CSF agents possess the ability to mobilize stem-cells from bone marrow and induce their differentiation into cardiomyocytes or endothelial cells when brought into contact with injured regions of the myocardium. However, clinical benefits of G-CSF use in damaged myocardium remain unclear and are the topic of expert discussion. The main goal of this review is to present relevant and up-to-date evidence on G-CSF therapy use in pre-clinical models and in humans and to provide a rationale for its potential clinical applications in the future.

Sex Differences in Heart Failure.

Heart failure (HF) represents a global pandemic health problem with a high impact on health-care costs, affecting about 26 million adults worldwide. The overall HF prevalence and incidence are ~2% and ~0.2% per year, respectively, in Western countries, with half of the HF population with reduced ejection fraction (HFpEF) and half with preserved (HFpEF) or mid-range ejection fraction (HFmrEF). Sex differences may exist in HF. More males have HFrEF or HFmrEF and an ischemic etiology, whereas more females have HFpEF and hypertension, diastolic dysfunction, and valvular pathologies as HF etiologies. Females are generally older, have a higher EF, higher frequency of HF-related symptoms, and lower NYHA functional status. Generally, it is observed that female HF patients tend to have more comorbidities such as atrial fibrillation, diabetes, hypertension, anemia, iron deficiency, renal disease, arthritis, frailty, depression, and thyroid abnormalities. However, overall, females have better prognosis in terms of mortality and hospitalization risk compared with men, regardless of EF. Potential sex differences in HF characteristics may be underestimated because of the underrepresentation of females in cardiovascular research and, in particular, the sex imbalance in clinical trial enrollment may avoid to identify sex-specific differences in treatments' benefit.

Outcomes of Surgery for Severe Aortic Regurgitation with Systolic Left Ventricular Dysfunction.

BACKGROUND AND AIM OF THE STUDY: Management of patients with aortic regurgitation (AR) and severe impairment of left ventricular (LV) function characterized by an ejection fraction (EF) ≤35% is challenging. Conflicting results regarding perioperative and long-term survival of these patients have been reported. The study aim was to compare in-hospital outcomes and long-term survival of patients with AR and severe LV dysfunction versus moderate dysfunction (35% 70 years and NYHA class III/IV symptoms were predictive of survival. CONCLUSIONS: In-hospital and long-term survival was similar in patients with severe LV dysfunction and with preserved or moderately reduced LV function. Positive reverse LV remodelling and improved LV function was evident at the two-year echocardiographic follow up in these patients, who should not be denied aortic valve surgery.