J. Cardiovasc. Dev. Dis., Volume 8, Issue 12 (December 2021) – 30 articles

Hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor is a recently introduced oral agent to treat renal anemia, but its clinical implications on renal functioning in patients with heart failure remains unknown. We studied an 81-year-old man with heart failure with mildly reduced ejection fraction, chronic kidney disease, and renal anemia. The seven-month HIF-PH inhibitor daprodustat treatment improved the hemoglobin level from 7.4 g/dL to 11.8 g/dL and estimated glomerular filtration ratio from 24 mL/min/1.73 m² to 35 mL/min/1.73 m² without any complications, including thromboembolic events. HIF-PH inhibitor might be a promising therapeutic tool to improve renal anemia and renal function in patients with heart failure, although large-scale studies are warranted to validate our findings. Full article

In this case report, we describe a complex case of a 67-year-old patient who was suffering from acute heart failure with electrical storm. Clinical case management was based on an integrated approach comprising two different procedures that were complementary and synergistic, and that allowed the patient to reach acute stabilization and to demonstrate mid-term clinical improvement. Complex clinical settings, such as electrical and hemodynamic instability, require complex solutions. The use of an integrated approach that allows physiopathological mechanisms to work together may be beneficial for these patients. Full article

Takayasu Arteritis (TA) is characterized by granulomatous panarteritis, vessel wall fibrosis, and irreversible vascular impairment. The aim of this study is to explore the usefulness of the Enhanced Liver Fibrosis score (ELF), procollagen-III aminoterminal propeptide (PIIINP), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), and hyaluronic acid (HA) in assessing vascular damage in TA patients. ELF, PIIINP, TIMP-1, and HA were measured in 24 TA patients, and the results were correlated with the clinical damage indexes (VDI and TADS), an imaging damage score (CARDS), and disease activity scores (NIH and ITAS2010). A mean ELF score 8.42 (±1.12) and values higher than 7.7 (cut-off for liver fibrosis) in 21/24 (87.5%) of patients were detected. The VDI and TADS correlated significantly to ELF (p < 0.01). Additionally, a strong association across ELF and CARDS (p < 0.0001), PIIINP and CARDS (p < 0.001), and HA and CARDS (p < 0.001) was observed. No correlations of the tested biomarkers with inflammatory parameters, NIH, and ITAS2010 scores were found. To our knowledge, this is the first study that suggests the association of the serum biomarkers PIIINP, HA, and ELF score with damage but not with disease activity in TA patients. The ELF score and PIIINP may be useful biomarkers reflecting an ongoing fibrotic process and quantifying vascular damage. Full article

Coronary artery ectasia (CAE) is a rare finding and is associated with poor clinical outcomes. However, prognostic factors are not well studied and no prognostication tool is available. In a derivation set comprising 729 consecutive CAE patients between January 2009 and June 2014, a nomogram was developed using Cox regression. Total of 399 patients from July 2014 to December 2015 formed the validation set. The primary outcome was 5-year major adverse cardiovascular events (MACE), a component of cardiovascular death and nonfatal myocardial infarction. Besides the clinical factors, we used quantitative coronary angiography (QCA) and defined QCA classification of four types, according to max diameter (< or ≥5 mm) and max length ratio (ratio of lesion length to vessel length, < or ≥1/3) of the dilated lesion. A total of 27 cardiovascular deaths and 41 nonfatal myocardial infarctions occurred at 5-year follow-up. The nomogram effectively predicted 5-year MACE risk using predictors including age, prior PCI, high sensitivity C-reactive protein, N-terminal pro-brain natriuretic peptide, and QCA classification (area under curve [AUC] 0.75, 95% CI 0.68–0.82 in the derivation set; AUC 0.71, 95% CI 0.56–0.86 in the validation set). Patients were classified as high-risk if prognostic scores were ≥155 and the Kaplan–Meier curves were well separated (log-rank p < 0.001 in both sets). Calibration curve and Hosmer–Lemeshow test indicated similarity between predicted and actual 5-year MACE survival (p = 0.90 in the derivation and p = 0.47 in the validation set). This study developed and validated a simple-to-use method for assessing 5-year MACE risk in patients with CAE. Full article

The aim of this study was to assess the factors associated with impaired vascular function in patients with poorly controlled type 2 diabetes (DM2) with and without overt cardiovascular disease (CVD). Ninety-five patients with DM2 and poor glycemic control were recruited and divided into two groups: Group 1, with known CVD (n = 38), and Group 2, without CVD (n = 57). Patients in Group 2 were further subdivided into those with short (<5 years, group 2b) and long (>5 years, group 2a) diabetes duration. Subclinical markers of atherosclerosis were assessed. Glycemic control was similar in the two groups (HbA1c: 9.2% (1.5) vs. 9.4% (1.8), p = 0.44). In Group 1, lower FMD (3.13 (2.16)% vs. 4.7 (3.4)%, p < 0.05) and higher cIMT (1.09 (0.3) mm vs. 0.96 (0.2) mm, p < 0.05) was seen compared with Group 2, whereas PWV was similar (12.1 (3.4) vs. 11.3 (3.0) m/s, p = 0.10). Patients in Group 2b had significantly lower PWV and cIMT and higher FMD compared to Group 1 (p < 0.05). Among patients with poorly controlled T2D, more pronounced vascular dysfunction was present in those with overt macrovascular disease. In patients with T2D without known CVD, vascular dysfunction was associated with disease duration. The use of vascular indices for cardiovascular risk stratification in patients with T2D requires further study. Full article

Cognitive impairment (CI) represents a common but often veiled comorbidity in patients with acute heart failure (AHF) that deserves more clinical attention. In the AHF setting, it manifests as varying degrees of deficits in one or more cognitive domains across a wide spectrum ranging from mild CI to severe global neurocognitive disorder. On the basis of the significant negative implications of CI on quality of life and its overwhelming association with poor outcomes, there is a compelling need for establishment of detailed consensus guidelines on cognitive screening methods to be systematically implemented in the population of patients with heart failure (HF). Since limited attention has been drawn exclusively on the field of CI in AHF thus far, the present narrative review aims to shed further light on the topic. The underlying pathophysiological mechanisms of CI in AHF remain poorly understood and seem to be multifactorial. Different pathophysiological pathways may come into play, depending on the clinical phenotype of AHF. There is some evidence that cognitive decline closely follows the perturbations incurred across the long-term disease trajectory of HF, both along the time course of stable chronic HF as well as during episodes of HF exacerbation. CI in AHF remains a rather under recognized scientific field that poses many challenges, since there are still many unresolved issues regarding cognitive changes in patients hospitalized with AHF that need to be thoroughly addressed. Full article

Laser balloon (LB) has emerged as an interesting strategy for pulmonary vein isolation in paroxysmal atrial fibrillation (AF). A third-generation LB has recently been developed, allowing a continuous ablation set. We aimed to compare the results from our center’s experience with second and third-generation LBs to a cohort of matched patients who had undergone radiofrequency ablation (RFA) with contact-force catheters. This retrospective monocenter case-control study included our first 50 LB paroxysmal AF ablations (26 second and 24 third-generation LB) and 50 RFA controls, matched on age, sex and left atrial dilation. The two groups had similar baseline parameters. LB procedures were significantly shorter than RFA (129 (110–160) vs. 160 (119–198) min, p = 0.007). During AF ablation, two major complications occurred in each group. At the one-year follow-up, AF recurrence was diagnosed in 7 (14%) of the LB group vs. 14 (28%) of the RFA group (p = 0.14). Moreover, we observed that third-generation LB procedures were associated with shorter laser applications (22 (19–29) vs. 69 (55–76) min, p < 0.001) and procedural durations (111 (100–128) vs. 151.5 (128.5–167) min, p < 0.001) compared to second-generation LB procedures. In the context of the major increase in the number of AF ablations, LB demonstrated consistent results in terms of clinical success, complications and also reduced procedure durations compared to RFA. Full article

Lipoprotein(a) [Lp(a)] levels are an independent risk factor for coronary artery disease (CAD). Two single-nucleotide polymorphisms (rs10455872, rs3798220) and number of KIV-2 repeats in the gene encoding Lp(a) (LPA) are associated with Lp(a) and CAD. Our aim was to investigate whether in patients with stable CAD and high Lp(a) levels these genetic variants are associated with increased Lp(a) and arterial wall properties. Blood samples underwent biochemical and genetic analyses. Ultrasound measurements for the functional and morphological properties of arterial wall were performed. Genotypes of rs10455872 and haplotypes AT and GT showed significant association with Lp(a) levels. Patients with GG showed significantly higher Lp(a) levels compared with those with AG genotype (2180 vs. 1391 mg/L, p = 0.045). Patients with no AT haplotype had significantly higher Lp(a) compared to carriers of one AT haplotype (2158 vs. 1478 mg/L, p = 0.023) or two AT haplotypes (2158 vs. 1487 mg/L, p = 0.044). There were no significant associations with the properties of the arterial wall. Lp(a) levels significantly correlated also with number of KIV-2 repeats (r = −0.601; p < 0.0001). In our patients, these two LPA polymorphisms and number of KIV-2 repeats are associated with Lp(a), but not arterial wall properties. Full article

Background: Optimal heart rate (HR) that associates with higher cardiac output and greater clinical outcomes in patients with cardiac amyloidosis remains unknown. Methods: Consecutive patients with sinus rhythm who were diagnosed with cardiac amyloidosis at our institute between February 2015 and February 2021 were retrospectively included. Ideal HR, at which E-wave and A-wave stand adjacent without any overlaps in the trans-mitral flow echocardiography, was calculated by the formula: 86.8−0.08 × deceleration time (msec). The association between optimal HR and cardiac death or heart failure readmission was investigated. Results: Ten patients (median 74 years old, 8 men) were included. On median, actual HR was 64 bpm and ideal HR was 69 bpm. An incidence rate of the primary endpoint in the sub-optimal HR group tended to be higher than optimal HR group: one of the four patients in optimal HR group had events (25%); two of the two patients in higher HR group had events (100%); two of the four patients in lower HR group had events (50%). Conclusions: The optimal HR was associated with greater clinical outcomes in patients with cardiac amyloidosis. The clinical impact of aggressive HR optimization in this cohort remains the next concern. Full article

The median survival of patients with heart transplants is relatively limited, implying one of the most relevant questions in the field—how to expand the lifespan of a heart allograft? Despite optimal transplantation conditions, we do not anticipate a rise in long-term patient survival in near future. In order to develop novel strategies for patient monitoring and specific therapies, it is critical to understand the underlying pathological mechanisms at cellular and molecular levels. These events are driven by innate immune response and allorecognition driven inflammation, which controls both tissue damage and repair in a spatiotemporal context. In addition to immune cells, also structural cells of the heart participate in this process. Novel single cell methods have opened new avenues for understanding the dynamics driving the events leading to allograft failure. Here, we review current knowledge on the cellular composition of a normal heart, and cellular mechanisms of ischemia-reperfusion injury (IRI), acute rejection and cardiac allograft vasculopathy (CAV) in the transplanted hearts. We highlight gaps in current knowledge and suggest future directions, in order to improve cellular and molecular understanding of failing heart allografts. Full article

There are still grey areas in the understanding of the myoarchitecture of the ventricular mass. This is despite the progress of investigation methods since the beginning of the 21st century (diffusion tensor magnetic resonance imaging, microcomputed tomography, and polarised light imaging). The objective of this article is to highlight the specificities and the limitations of polarised light imaging (PLI) of the unstained myocardium embedded in methyl methacrylate (MMA). Thus, to better differentiate our method from other PLI modes, we will refer to it by the acronym PLI-MMA. PLI-MMA shows that the myosin mesh of the compact left ventricular wall behaves like a biological analogous of a nematic chiral liquid crystal. Results obtained by PLI-MMA are: the main direction of the myosin molecules contained in an imaged voxel, the crystal liquid director n, and a regional isotropy index RI that is an orientation tensor, the equivalent of the crystal liquid order parameter. The vector n is collinear with the first eigenvector of diffusion tensor imaging (DTI-MRI). The RI has not been confounded with the diffusion tensor of DTI that gives information about the three eigenvectors of the ellipsoid of diffusion. PLI-MMA gives no information about the collagen network. The physics of soft matter has allowed the revisiting of Streeter’s conjecture on the myoarchitecture of the compact left ventricular wall: “geodesics on a nested set of toroidal surfaces”. Once the torus topology is understood, this characterisation of the myoarchitecture is more accurate and parsimonious than former descriptions. Finally, this article aims to be an enthusiastic invitation to a transdisciplinary approach between physicists of liquid crystals, anatomists, and specialists of imaging. Full article

Ethical issues restrict research on human embryos, therefore calling for in vitro models to study human embryonic development including the formation of the first functional organ, the heart. For the last five years, two major models have been under development, namely the human gastruloids and the cardiac organoids. While the first one mainly recapitulates the gastrulation and is still limited to investigate cardiac development, the second one is becoming more and more helpful to mimic a functional beating heart. The review reports and discusses seminal works in the fields of human gastruloids and cardiac organoids. It further describes technologies which improve the formation of cardiac organoids. Finally, we propose some lines of research towards the building of beating mini-hearts in vitro for more relevant functional studies. Full article

Background: The fetal origins hypothesis have associated early life exposures with the development of adverse health outcomes in adulthood. Season of birth has been shown to be associated with overall and cardiovascular mortality. Methods: We performed a retrospective database study to explore the association between season of birth and mortality in patients with atrial fibrillation. Results: A total of 8962 patients with AF were identified in the database with 1253 deaths recorded. AF patients born in spring and summer had a higher mortality rate when compared to those born in autumn and winter (hazard ratio (HR) 1.13, 95% confidence interval (CI) 1.01–1.26, p = 0.03). This effect was consistent in the male subgroup (HR 1.25, 95% CI 1.03–1.51, p = 0.02 for males born in spring; HR 1.24, 95% CI 1.03–1.51, p = 0.03 for males born in summer when compared to winter as the reference) but not in females (HR 1.02, 95% CI 0.79–1.31, p = 0.88 for females born in spring; HR 1.11, 95% CI 0.87–1.42, p = 0.39 for females born in summer when compared to winter as the reference). Results persisted after adjustment for baseline characteristics and clinical risk profile. A similar pattern was observed with cardiovascular mortality. Conclusion: Birth in spring or summer is associated with a higher risk of cardiovascular mortality in male AF patients, but not in females. This could be related to the underlying differences in rates of major adverse clinical events between genders. Further studies should aim at clarifying the mechanisms behind this association, which may help us understand the higher level of risk in female patients with AF. Full article

Premature ventricular contractions (PVCs) are common and generally benign in childhood and tend to resolve spontaneously in most cases. When PVCs occur frequently, an arrhythmia-induced cardiomyopathy may be present requiring medical or catheter ablation. PVCs are only rarely the manifestation of a cardiomyopathy. The purpose of this review is to provide some tips and tricks to raise the suspicion of a cardiac disease based on the presence and characteristics of PVCs in children. Full article

Common arterial trunk (CAT) is a rare congenital heart disease that is commonly included into the spectrum of conotruncal heart defects. CAT is rarely associated with functionally univentricular hearts, and only few cases have been described so far. Here, we describe the anatomical characteristics of CAT associated with a univentricular heart diagnosed in children and fetuses referred to our institution, and we completed the anatomical description of this rare condition through an extensive review of the literature. The complete cohort ultimately gathered 32 cases described in the literature completed by seven cases from our unit (seven fetuses and one child). Four types of univentricular hearts associated with CAT were observed: tricuspid atresia or hypoplastic right ventricle in 16 cases, mitral atresia or hypoplastic left ventricle in 12 cases, double-inlet left ventricle in 2 cases, and unbalanced atrioventricular septal defect in 9 cases. Our study questions the diagnosis of CAT as the exclusive consequence of an anomaly of the wedging process, following the convergence between the embryonic atrioventricular canal and the common outflow tract. We confirm that some forms of CAT can be considered to be due to an arrest of cardiac development at the stages preceding the convergence. Full article

Controversies have been raised regarding the prevalence and potential clinical significance of mitral annular disjunction (MAD). We aim to address the anatomic characteristics of MAD and their association, if any, on survival. We retrospectively reviewed 1373 consecutive dissected hearts (1017 men, mean age at death 44.9 ± 0.4 y) and frequently detected MAD (median disjunctional length: 2.0 mm, range: 1.5 mm~8.5 mm), with the prevalence of 92.1% over the entire mitral annulus and 74.9% within the posterior annulus (pMAD). The presence of pMAD was associated with increased all-cause mortality (45 y vs. 49 y, hazard ratio [HR]: 1.28, 95% confidence interval [CI]: 1.11~1.47, p < 0.001), which persisted in the context of cardiovascular diseases (CVDs; 46 y vs. 51 y, HR: 1.33, 95% CI: 1.14~1.56, p < 0.001) but was insignificant in those without CVDs. Compared to those without pMAD, individuals with pMAD affecting the entire posterior annulus or having a mean standardized length of ≥1.78 showed other clinically significant cardiovascular phenotypes, including the enlargement of aortic annular circumferences and a higher occurrence of thoracic aortic aneurysm/dissection. This largest series of autopsies show that MAD is a common phenotype that may exert additive influence on the survival of individuals. It is necessary to establish a precise classification and stratification of MAD. Full article

Endoglin is a 180 kDa transmembrane glycoprotein that was demonstrated to be present in two different endoglin forms, namely membrane endoglin (Eng) and soluble endoglin (sEng). Increased sEng levels in the circulation have been detected in atherosclerosis, arterial hypertension, and type II diabetes mellitus. Moreover, sEng was shown to aggravate endothelial dysfunction when combined with a high-fat diet, suggesting it might be a risk factor for the development of endothelial dysfunction in combination with other risk factors. Therefore, this study hypothesized that high sEng levels exposure for 12 months combined with aging (an essential risk factor of atherosclerosis development) would aggravate vascular function in mouse aorta. Male transgenic mice with high levels of human sEng in plasma (Sol-Eng⁺) and their age-matched male transgenic littermates that do not develop high soluble endoglin (Control) on a chow diet were used. The aging process was initiated to contribute to endothelial dysfunction/atherosclerosis development, and it lasted 12 months. Wire myograph analysis showed impairment contractility in the Sol-Eng⁺ group when compared to the control group after KCl and PGF_2α administration. Endothelium-dependent responsiveness to Ach was not significantly different between these groups. Western blot analysis revealed significantly decreased protein expression of Eng, p-eNOS, and ID1 expression in the Sol-Eng⁺ group compared to the control group suggesting reduced Eng signaling. In conclusion, we demonstrated for the first time that long-term exposure to high levels of sEng during aging results in alteration of vasoconstriction properties of the aorta, reduced eNOS phosphorylation, decreased Eng expression, and altered Eng signaling. These findings suggest that sEng can be considered a risk factor for the development of vascular dysfunction during aging and a potential therapeutical target for pharmacological intervention. Full article

Myocardial infarction is one of the largest contributors to cardiovascular disease and reduces the ability of the heart to pump blood. One promising therapeutic approach to address the diminished function is the use of cardiac patches composed of biomaterial substrates and cardiac cells. These patches can be enhanced with the application of an auxetic design, which has a negative Poisson’s ratio and can be modified to suit the mechanics of the infarct and surrounding cardiac tissue. Here, we examined multiple auxetic models (orthogonal missing rib and re-entrant honeycomb in two orientations) with tunable mechanical properties as a cardiac patch substrate. Further, we demonstrated that 3D printing based auxetic cardiac patches of varying thicknesses (0.2, 0.4, and 0.6 mm) composed of polycaprolactone and gelatin methacrylate can support induced pluripotent stem cell-derived cardiomyocyte function for 14-day culture. Taken together, this work shows the potential of cellularized auxetic cardiac patches as a suitable tissue engineering approach to treating cardiovascular disease. Full article

Mitral stenosis is an important cause of heart valve disease globally. Echocardiography is the main imaging modality used to diagnose and assess the severity and hemodynamic consequences of mitral stenosis as well as valve morphology. Transthoracic echocardiography (TTE) is sufficient for the management of most patients. The focus of this review is the role of current two-dimensional (2D) and three-dimensional (3D) echocardiographic imaging for the evaluation of mitral stenosis. Full article

Atheroprotective properties of human plasma high-density lipoproteins (HDLs) are determined by their involvement in reverse cholesterol transport (RCT) from the macrophage to the liver. ABCA1, ABCG1, and SR-BI cholesterol transporters are involved in cholesterol efflux from macrophages to lipid-free ApoA-I and HDL as a first RCT step. Molecular determinants of RCT efficiency that may possess diagnostic and therapeutic meaning remain largely unknown. This review summarizes the progress in studying the genomic variants of ABCA1, ABCG1, and SCARB1, and the regulation of their function at transcriptional and post-transcriptional levels in atherosclerosis. Defects in the structure and function of ABCA1, ABCG1, and SR-BI are caused by changes in the gene sequence, such as single nucleotide polymorphism or various mutations. In the transcription initiation of transporter genes, in addition to transcription factors, long noncoding RNA (lncRNA), transcription activators, and repressors are also involved. Furthermore, transcription is substantially influenced by the methylation of gene promoter regions. Post-transcriptional regulation involves microRNAs and lncRNAs, including circular RNAs. The potential biomarkers and targets for atheroprotection, based on molecular mechanisms of expression regulation for three transporter genes, are also discussed in this review. Full article

Background: Post-operative (POP) atrial fibrillation (AF) is frequent in patients who undergo cardiac surgery. However, its prognostic impact in the long term remains unclear. Methods: We followed 1386 patients who underwent cardiac surgery for an average of 10 ± 3 years. According to clinical history of AF before and after surgery, four subgroups were identified: (1) patients with no history of AF and without episodes of AF during the first 30 days after surgery (control or Group 1, n = 726), (2) patients with no history of AF before surgery in whom new-onset POP AF was detected during the first 30 days after surgery (new-onset POP AF or Group 2, n = 452), (3) patients with a history of paroxysmal/persistent AF before cardiac surgery (Group 3, n = 125, including 87 POP AF patients and 38 who did not develop POP AF), and (4) patients with permanent AF at the time of cardiac surgery (Group 4, n = 83). All-cause mortality was the primary outcome of the study. We tested the associations of potential determinants with all-cause mortality using univariable and multivariable statistical analyses. Results: Overall, 473 patients (34%) died during follow-up. After adjustment for multiple confounders, new-onset POP AF (hazard ratio (HR) = 1.31, 95% confidence interval (CI): 0.90–1.89; p = 0.1609), history of paroxysmal/persistent AF before cardiac surgery (HR = 1.33, 95% CI: 0.71–2.49; p = 0.3736), and permanent AF (Group 4) (HR = 1.55, 95% CI 0.82–2.95; p = 0.1803) were not associated with a significantly increased risk of mortality when compared with Group 1 (patients with no history of AF and without episodes of AF during the first 30 days after surgery). In new-onset POP AF patients, oral anticoagulation was not associated with mortality (HR = 1.13, 95% CI: 0.83–1.54; p = 0.4299). Conclusions: In this cohort of patients who underwent different types of heart surgery, POP AF was not associated with an increased risk of mortality. In this setting, the role of long-term anticoagulation remains unclear. Full article

The long-term lead stability and echocardiographic outcomes of left bundle branch area pacing (LBBAP) are not fully understood. This study aimed to observe the mid-long-term clinical impact of LBBAP compared to right ventricular pacing (RVP). Consecutive bradycardia patients undergoing LBBAP or RVP were enrolled. Pacing and electrophysiological characteristics, echocardiographic measurements, and procedural complications were prospectively recorded at baseline and follow-up. LBBAP was successful in 376 of 406 patients (92.6%), while 313 patients received RVP. During a mean follow-up of 13.6 ± 7.8 months, LBBAP presented with similar pacing parameters and complications to RVP, except a significantly narrower paced QRS duration (115.7 ± 12.3 ms vs. 148.0 ± 18.0 ms, p < 0.001). In 228 patients with ventricular pacing burden >40%, LBBAP at last follow-up resulted in decreased left atrial diameter (LAD) (40.1 ± 8.5 mm vs. 38.5 ± 8.0 mm, p < 0.001) while RVP produced decreased left ventricular ejection fraction (62.7 ± 4.8% vs. 60.5 ± 6.9%, p < 0.001) when compared to baseline. After adjusting for age, the presence of atrial fibrillation, and other clinical factors, LBBAP was still associated with a decrease in LAD (−1.601, 95% CI −3.094–−0.109, p = 0.036). We conclude that LBBAP might result in more preserved echocardiographic outcomes than RVP. Full article

A high percentage of patients with COVID-19 (coronavirus disease 2019) have previous cardiovascular disease (CVD). The findings presented here came from an epidemiological population-based registry study (real-world data) that enrolled all in-hospital COVID-19 patients with previous CVD from 1 March to 31 May 2020. Death, other comorbidities, hospital stay variables, ventilation type, and main clinical outcomes were evaluated. In Castile and Leon, 35.83% of the 7307 in-hospital COVID-19 patients who participated in this study had previous CVD, particularly arrhythmias (48.97%), cerebrovascular disease (25.02%), ischemic heart disease (22.8%), and chronic heart failure (20.82%). Of the patients, 21.36% were men and more than 90% were over 65 years of age, and the mortality rate achieved 32.93%. The most used medicines were antibiotics (91.41%), antimalarials (73.3%), steroids (46.64%), and antivirals (43.16%). The main predictors of death were age over 65 years (OR: 5), ventilation needs (OR: 2.81), treatment with anti-SIRS (systemic inflammatory response syndrome) medicines (OR: 1.97), antivirals (OR: 1.74) or steroids (OR: 1.68), SIRS (OR: 5.75), SARS (severe acute respiratory syndrome) (OR: 2.44), or AKI (acute kidney injury) (OR: 1.63) occurrence. Chronic heart failure and cerebrovascular disease were associated with a worse clinical course of COVID-19, especially in men older than 65 years with diabetes who developed SIRS, SARS, or AKI. Full article

Coronary heart disease is the leading cause of death and disability worldwide. Traditionally, cardiac rehabilitation programmes are offered after cardiac events to aid recovery, improve quality of life, and reduce adverse events. The objective of this review was to assess the health-related quality of life, after a supervised cardiac rehabilitation programme, of patients who suffered a myocardial infarction. A systematic review was carried out in the CINAHL, Cochrane, LILACS, Medline, Scopus, and SciELO databases, according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. Randomised controlled trials were selected. Meta-analyses were performed for the Short Form Health Survey SF-36, Myocardial Infarction Dimensional Assessment Scale (MIDAS), MacNew Heart Disease-Health-Related Quality of Life (HRQL) questionnaire, and European Quality of Life-Visual Analogue Scale (EuroQol-VAS) with the software Cochrane RevMan Web. Ten articles were found covering a total of 3577 patients. In the meta-analysis, the effect size of the cardiac rehabilitation programme was statistically significant in the intervention group for physical activity, emotional reaction, and dependency dimensions of the MIDAS questionnaire. For the control group, the score improved for SF-36 physical functioning, and body pain dimensions. The mean difference between the control and intervention group was not significant for the remaining dimensions, and neither for the MacNew Heart Disease-HRQL and EuroQol-VAS questionnaires. Supervised cardiac rehabilitation programmes were effective in improving health-related quality of life, however, there was a potential variability in the interventions; therefore, the results should be interpreted with caution. This study supports the importance of providing care and evaluating interventions via the supervision of trained health professionals, and further randomised clinical trials are needed to analyse the positive changes in mental and physical health outcomes. Full article

Although 18–45-year-old (y-o) patients represent a significant proportion of patients hospitalized for COVID-19, data concerning the young population remain scarce. The Critical COVID France (CCF) study was an observational study including consecutive patients hospitalized for COVID-19 in 24 centers between 26 February and 20 April 2020. The primary composite outcome included transfer to the intensive care unit (ICU) or in-hospital death. Secondary outcomes were cardiovascular (CV) complications. Among 2868 patients, 321 (11.2%) patients were in the 18–45-y-o range. In comparison with older patients, young patients were more likely to have class 2 obesity and less likely to have hypertension, diabetes and dyslipidemia. The primary outcome occurred less frequently in 18–45-y-o patients in comparison with patients > 45 years old (y/o) (16.8% vs. 30.7%, p < 0.001). The 18–45-y-o patients presented with pericarditis (2.2% vs. 0.5%, p = 0.003) and myocarditis (2.5% vs. 0.6%, p = 0.002) more frequently than patients >45 y/o. Acute heart failure occurred less frequently in 18–45-y-o patients (0.9% vs. 7.2%, p < 0.001), while thrombotic complications were similar in young and older patients. Whereas both transfer to the ICU and in-hospital death occurred less frequently in young patients, COVID-19 seemed to have a particular CV impact in this population. Full article

The purpose of this study was to compare the acute cardiorespiratory responses and time spent above different %VO_2peak intensities between three “iso-work” protocols: (a) a high intensity interval training protocol (HIIT), (b) a higher intensity continuous protocol (CON₇₀) and (c) a lower intensity continuous protocol (CON₅₀) in patients with chronic heart failure (CHF). Ten male CHF patients (aged 55.1 ± 16.2 years) performed in separate days a single session of a HIIT protocol consisted of 4 sets × 4 min cycling at 80% VO_2peak with 3 min of recovery at 50% VO_2peak, a CON₇₀ protocol corresponding to 70% VO_2peak and a CON₅₀ protocol corresponding to 50% VO_2peak. Cardiopulmonary data were collected by an online gas analysis system. The HIIT and CON₇₀ elicited higher cardiorespiratory responses compared to CON₅₀ with no differences between them (p > 0.05). In HIIT and CON₇₀, patients exercised longer at >80% and >90% VO_2peak. The completion rate was 100% for the three protocols. Not any adverse events were observed in either protocol. Both HIIT and CON₇₀ elicited a stronger physiological stimulus and required shorter time than CON₅₀. Both HIIT and CON₇₀ also induced comparable hemodynamic responses and ventilatory demand. Full article

Intraoperative assessment of graft patency is pivotal for successful coronary revascularization. In the present study we aimed to propose a new, easy to perform tool to assess anastomotic quality intraoperatively, and to investigate its potential reliability in predicting early graft failure. Intraoperative graft flowmetry of 63 consecutive patients undergoing CABG were prospectively collected. Transit time flowmetry and its derivatives were recorded. Coronary resistances were calculated according to Hagen–Poiseuille equation both during cardioplegic arrest and after withdrawal from cardiopulmonary bypass. Angiographic evidence of graft occlusion at follow-up was cross-checked with intraoperative recordings. After a mean follow-up of 10.4 ± 6.0 months, 22 grafts were studied, and occlusion was documented in five (22.7%). Occluded grafts showed lower flows and higher resistances recorded during aortic cross-clamping. Coronary resistances, recorded during aortic cross-clamping, greater than 2.0 mmHg/mL/min, showed a sensitivity of 80% and a specificity of 100% to predict graft failure. We propose the routine recording of coronary resistances during aortic cross-clamping as an additional tool to overcome the acknowledged limitation of TTF to predict graft occlusion at 1 year. Full article

Recent meta-analysis studies have reported that metabolic comorbidities such as diabetes, obesity, dyslipidaemia and hypertension are associated with higher risk of severe acute respiratory syndrome (SARS) and mortality in patients with COVID-19. This meta-analysis aims to investigate the relationship between metabolic syndrome (MetS) and its components with SARS and mortality in COVID-19 patients. Methods: A systematic search was conducted in the several databases up until 1 September 2021. Primary observational longitudinal studies published in peer review journals were selected. Two independent reviewers performed title and abstract screening, extracted data and assessed the risk of bias using the Newcastle–Ottawa Scale. Results: The random effects meta-analysis showed that MetS was significantly associated with SARS with a pooled OR (95% CI) of 3.21 (2.88–3.58) and mortality with a pooled OR (95% CI) of 2.32 (1.16–4.63). According to SARS, the pooled OR for MetS was 2.19 (1.71–2.67), p < 0.001; significantly higher than the hypertension component. With regard to mortality, although the pooled OR for MetS was greater than for its individual components, no significant differences were observed. Conclusions: this meta-analysis of cohort studies, showed that MetS is better associated to SARS and mortality in COVID-19 patients than its individual components. Full article

Despite the critical feature of heparin-induced thrombocytopenia (HIT) for patients on mechanical circulatory support, reports on its incidence and outcome are still scarce. Thus, we report on clinical features of HIT in patients under Impella 5.0 or 5.5 (Abiomed Inc., Danvers, MA, USA) (Impella 5+) support for acute cardiogenic shock (CS) by focusing on observed thrombotic events. Between November 2018 and December 2020, a total of 56 consecutive patients were enrolled in a single-center retrospective study. A total of 21 patients (37.5%) were tested for HIT, and 6 (10.7%) proved positive for HIT at 10.5 ± 2.89 days after the first heparin administration during current admission. Interestingly, thrombocyte counts dropped under Impella support in all groups (all cases, no HIT test, and HIT negative group: p < 0.001, HIT-positive group: p = 0.001). All HIT-positive patients were switched from heparin to argatroban. HIT-associated thrombotic events were observed in two cases resulting in Impella dysfunction due to pump thrombosis (n = 1) and left ventricular (LV) thrombus formation (n = 1). Under large Impella support, the prevalence of HIT was relatively high. Further, thrombocytopenia does not deliver a high specificity in the setting of Impella 5+ support. Considering HIT manifestation, a routine HIT test may be considered to avoid critical thrombotic adverse events. Full article

The Popeye domain-containing (POPDC) gene family, consisting of Popdc1 (also known as Bves), Popdc2, and Popdc3, encodes transmembrane proteins abundantly expressed in striated muscle. POPDC proteins have recently been identified as cAMP effector proteins and have been proposed to be part of the protein network involved in cAMP signaling. However, their exact biochemical activity is presently poorly understood. Loss-of-function mutations in animal models causes abnormalities in skeletal muscle regeneration, conduction, and heart rate adaptation after stress. Likewise, patients carrying missense or nonsense mutations in POPDC genes have been associated with cardiac arrhythmias and limb-girdle muscular dystrophy. In this review, we introduce the POPDC protein family, and describe their structure function, and role in cAMP signaling. Furthermore, the pathological phenotypes observed in zebrafish and mouse models and the clinical and molecular pathologies in patients carrying POPDC mutations are described. Full article