The importance of gut microbiota in health and disease is being highlighted by numerous research groups worldwide. Atherosclerosis, the leading cause of heart disease and stroke, is responsible for ...about 50% of all cardiovascular deaths. Recently, gut dysbiosis has been identified as a remarkable factor to be considered in the pathogenesis of cardiovascular diseases (CVDs). In this review, we briefly discuss how external factors such as dietary and physical activity habits influence host-microbiota and atherogenesis, the potential mechanisms of the influence of gut microbiota in host blood pressure and the alterations in the prevalence of those bacterial genera affecting vascular tone and the development of hypertension. We will also be examining the microbiota as a therapeutic target in the prevention of CVDs and the beneficial mechanisms of probiotic administration related to cardiovascular risks. All these new insights might lead to novel analysis and CVD therapeutics based on the microbiota.
Background
Leadless pacemakers were developed to reduce complications associated with transvenous pacemaker implantation and long‐term follow‐up. Existing international guidelines lack detailed ...instructions on patients suitable for leadless pacemaker implantation. Our aim was to develop a consensus document that provides medical guidance for all health professionals involved in the indication and implantation of Transcatheter Pacing System single‐chamber device (VR leadless) pacemakers for patients with atrial fibrillation or in sinus rhythm.
Methods
A panel of experts, including interventional and non‐interventional cardiologists, used the Research ANd Development/University of California at Los Angeles (RAND/UCLA) method to rate the appropriateness of leadless pacemaker implantation for 64 scenarios in patients with atrial fibrillation and 192 scenarios in sinus rhythm. The scenarios were rated individually and again during a moderated group session. Median ratings and level of agreement were calculated to classify each scenario as appropriate, inappropriate, or questionable.
Results
This consensus statement, based on available literature and the experts’ opinions, summarizes recommendations for standardizing and optimizing leadless pacemaker implantation. The limitation for vascular access via the superior vena cava was the most influential variable when indicating leadless pacemaker implantation in both patients with atrial fibrillation and patients in sinus rhythm.
Conclusions
Life expectancy, risk of infection, prosthetic valve, left ventricular ejection fraction (LVEF), limitation for vascular access via the superior vena cava, and mobility and exercise capacity determine who is advised to undergo VR leadless pacemaker implantation. More prospective studies are needed to optimize existing recommendations.
Cardiac channelopathies are a frequent cause of sudden cardiac death (SCD) and often manifest with convulsive syncope, leading to a misdiagnosis of epilepsy. We aim to evaluate the clinical impact of ...epilepsy misdiagnosis in a cohort of patients with cardiac channelopathies.
Fifty probands/families with a cardiac channelopathy were included. We retrospectively collected information from medical records to identify all patients who presented with convulsive syncope and were diagnosed with epilepsy after neurological evaluation. Clinical data and outcome were compared with those of patients without a previous epilepsy diagnosis.
Eight patients had a previous diagnosis of epilepsy. At first episode, 3 of them presented a positive family history of SCD and 5 showed a pathological electrocardiogram; half presented with sudden cardiac arrest (SCA) and the rest with recurrent syncope despite treatment with 1 or more anti-epileptic drugs. Five patients had long QT syndrome, 2 had catecholaminergic polymorphic ventricular tachycardia, and 1 had Brugada syndrome. Epilepsy misdiagnosis was associated with an increased risk of SCA/SCD (OR 6.92, P = .04), a delay of 12 years (P = .047) in correct diagnosis, and a delay from first symptom to channelopathy diagnosis of 18.45 years (P < .0001).
Cardiac channelopathy patients can be misdiagnosed with epilepsy. This involves a delayed diagnosis, a delay from the first symptom to a correct diagnosis, and an increased risk of SCA/SCD.
Desmin (
) mutations cause severe skeletal and cardiac muscle disease with heterogeneous phenotypes. Recently,
mutations were described in patients with inherited arrhythmogenic right ventricular ...cardiomyopathy/dysplasia, although their cellular and molecular pathomechanisms are not precisely known. Our aim is to describe clinically and functionally the novel
-p.Glu401Asp mutation as a cause of inherited left ventricular arrhythmogenic cardiomyopathy/dysplasia.
We identified the novel
mutation p.Glu401Asp in a large Spanish family with inherited left ventricular arrhythmogenic cardiomyopathy/dysplasia and a high incidence of adverse cardiac events. A full clinical evaluation was performed on all mutation carriers and noncarriers to establish clinical and genetic cosegregation. In addition, desmin, and intercalar disc-related proteins expression were histologically analyzed in explanted cardiac tissue affected by the
mutation. Furthermore, mesenchymal stem cells were isolated and cultured from 2 family members with the
mutation (1 with mild and 1 with severe symptomatology) and a member without the mutation (control) and differentiated ex vivo to cardiomyocytes. Then, important genes related to cardiac differentiation and function were analyzed by real-time quantitative polymerase chain reaction. Finally, the p.Glu401Asp mutated
gene was transfected into cell lines and analyzed by confocal microscopy.
Of the 66 family members screened for the
-p.Glu401Asp mutation, 23 of them were positive, 6 were obligate carriers, and 2 were likely carriers. One hundred percent of genotype-positive patients presented data consistent with inherited arrhythmogenic cardiomyopathy/dysplasia phenotype with variable disease severity expression, high-incidence of sudden cardiac death, and absence of skeletal myopathy or conduction system disorders. Immunohistochemistry was compatible with inherited arrhythmogenic cardiomyopathy/dysplasia, and the functional study showed an abnormal growth pattern and cellular adhesion, reduced desmin RNA expression, and some other membrane proteins, as well, and desmin aggregates in transfected cells expressing the mutant desmin.
The
-p.Glu401Asp mutation causes predominant inherited left ventricular arrhythmogenic cardiomyopathy/dysplasia with a high incidence of adverse clinical events in the absence of skeletal myopathy or conduction system disorders. The pathogenic mechanism probably corresponds to an alteration in desmin dimer and oligomer assembly and its connection with membrane proteins within the intercalated disc.
SARS-CoV-2 is a rapidly evolving pandemic causing great morbimortality. Medical therapy with hydroxicloroquine, azitromycin and protease inhibitors is being empirically used, with reported data of ...QTc interval prolongation. Our aim is to assess QT interval behaviour in a not critically ill and not monitored cohort of patients. We evaluated admitted and ambulatory patients with COVID-19 patients with 12 lead electrocardiogram at 48 h after treatment initiation. Other clinical and analytical variables were collected. Statistical analysis was performed to assess the magnitude of the QT interval prolongation under treatment and to identify clinical, analytical and electrocardiographic risk markers of QT prolongation independent predictors. We included 219 patients (mean age of 63.6 ± 17.4 years, 48.9% were women and 16.4% were outpatients. The median baseline QTc was 416 ms (IQR 404-433), and after treatment QTc was prolonged to 423 ms (405-438) (P < 0.001), with an average increase of 1.8%. Most of the patients presented a normal QTc under treatment, with only 31 cases (14.1%) showing a QTc interval > 460 ms, and just one case with QTc > 500 ms. Advanced age, longer QTc basal at the basal ECG and lower potassium levels were independent predictors of QTc interval prolongation. Ambulatory and not critically ill patients with COVID-19 treated with hydroxychloroquine, azithromycin and/or antiretrovirals develop a significant, but not relevant, QT interval prolongation.
Unexplained cardiac arrest (UCA) can be caused by low-penetrance genetic disorders. The aim of this cross-sectional study is to assess the usefulness of a new diagnostic protocol: Thirty-five ...patients were recruited from 9 Spanish centers. Electrocardiogram, echocardiogram, and coronary catheterization were used to rule out electrical or structural heart disease in all subjects. Patients underwent pharmacologic tests with epinephrine and flecainide, followed by assessment of family members using electrocardiogram and echocardiogram, and next-generation genetic sequencing to analyze 126 genes if all the other test results were negative. A firm diagnosis of channelopathy required phenotypic proof of the condition in unmasking tests, the presence of a pathogenic variant consistent with the phenotype observed, and/or co-segregation of the mutation found in a family member's phenotype. A firm diagnosis was made in 18 cases. The diagnoses were 7 Brugada syndrome, 5 catecholaminergic polymorphic ventricular tachycardia, 3 long QT syndrome, 2 early repolarization syndrome, and 1 short QT syndrome. Pharmacologic testing was the most frequent method of diagnosis. In 5 cases, the diagnosis was made based on positive genetic testing without phenotypic alterations. In conclusion, this sequential diagnostic protocol allows diagnoses to be made in approximately half of the UCA cases. These diagnoses are low clinical penetrance channelopathies. If interpreted carefully, genetic tests can be a useful tool for diagnosing UCA without a phenotype.
Premature ventricular complex (PVC) ablation has been shown to improve left ventricular ejection fraction (LVEF) and New York Heart Association functional class in patients with left ventricular ...dysfunction. Both are considered key variables in predicting risk of sudden cardiac death.
The objective of this study was to assess whether ablation might remove the primary prevention (PP) implantable cardioverter-defibrillator (ICD) indication in patients with frequent PVC.
Sixty-six consecutive patients with PP-ICD indication and frequent PVC 33 (50%) men; mean age 53 ± 13 years; 11 (17%) with ischemic heart disease underwent PVC ablation. The ICD was withheld and the indication was reevaluated at 6 and 12 months.
LVEF progressively improved from 28% ± 4% at baseline to 42% ± 12% at 12 months (P < .001). New York Heart Association functional class improved from 2 patients with NYHA functional class I (3%) at baseline to 35 (53%) at 12 months (P < .001). The brain natriuretic peptide level decreased from 246 ± 187 to 176 ± 380 pg/mL (P = .004). The PP-ICD indication was removed in 42 patients (64%) during follow-up, from 38 (92%) of them at 6 months, showing an independent association with baseline PVC burden and successful sustained ablation. In patients with successful sustained ablation, a cutoff value of 13% PVC burden had a sensitivity of 100% and a specificity of 93% (area under the curve 99%) for removing ICD indication postablation. No sudden cardiac deaths or malignant ventricular arrhythmias were observed.
In patients with frequent PVC and PP-ICD indication, ablation improves LVEF and, in most cases, allows removal of the indication. Withholding the ICD and reevaluating within 6 months of ablation seems to be a safe and appropriate strategy.
The treatment of patients with bifascicular block (BFB) and syncope in the absence of structural heart disease (SHD) is not well defined. The objective of our study is to compare pacemaker empirical ...implantation with the use of electrophysiological studies (EPS). This is a prospective cohort study that included 77 patients with unexplained cardiogenic syncope and BFB without structural heart disease between 1997 and 2012. Two groups: 36 patients received empirical pacemakers (Group A) and 41 underwent EPS (Group B) to guide their treatment. The incidence of syncope recurrence and atrioventricular block was lower in group A. Mortality and complication rates were similar between both groups. Multivariate analysis demonstrated a higher number of events (combined endpoint) in group B. Our study shows that treatment according to EPS does not improve the results of a treatment strategy based on empirical pacemaker.
Genetic variants that result in truncation in desmoplakin (DSP) are a known cause of arrhythmogenic cardiomyopathy (AC). In homozygous carriers, the combined involvement of skin and heart muscle is ...well defined, however, this is not the case in heterozygous carriers. The aim of this work is to describe cutaneous findings and analyze the molecular and ultrastructural cutaneous changes in this group of patients. Four women and eight men with a mean age of 48 ± 14 years were included. Eight met definitive criteria for AC, one was borderline and three were silent carriers. No relevant macroscopic changes in skin and hair were detected. However, significantly lower skin temperature (29.56 vs. 30.97 °C, p = 0.036) and higher transepidermal water loss (TEWL) (37.62 vs. 23.95 g m 2 h 1, p = 0.028) were observed compared to sex- and age-matched controls. Histopathology of the skin biopsy showed widening of intercellular spaces and acantholysis of keratinocytes in the spinous layer. Immunohistochemistry showed a strongly reduced expression of DSP in all samples. Trichogram showed regular nodules (thickening) compatible with pseudomonilethrix. Therefore, regardless of cardiac involvement, heterozygous patients with truncation-type variants in DSP have lower skin temperature and higher TEWL, constant microscopic skin involvement with specific patterns and pseudomonilethrix in the trichogram.
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