Electrocardiogram in Friedreich's ataxia: A short-term surrogate endpoint for treatment efficacy.

Friedreich's ataxia is a rare degenerative neuromuscular disorder, caused by a homozygous GAA triplet repeat expansion in the frataxin (FXN) gene, with a broad clinical phenotype characterized by progressive gait and limb ataxia, dysarthria, and loss of lower limb reflexes; cardiac involvement is represented by hypertrophic cardiomyopathy, ventricular arrhythmias, and sudden cardiac deaths. Currently, no definite therapy is available, while many drugs are under investigation; for this reasons, we need markers of short- and long-term treatment efficacy acting on different tissue for trial evaluation. We describe the case of a 21-year-old patient affected by Friedreich's ataxia on wheel-chair, with initial cardiac involvement and electrocardiographic features characterized by thiamine treatment-related negative T wave and QTc variations. We discuss plausible physiopathology and potential ECG role implications as an intermediate marker of treatment response in future clinical trials considering patients affected by Friedreich's ataxia.

Double missense mutations in cardiac myosin-binding protein C and myopalladin genes: A case report with diffuse coronary disease, complete atrioventricular block, and progression to dilated cardiomyopathy.

Cardiomyopathies caused by double gene mutations are rare but conferred a remarkably increased risk of end-stage progression, arrhythmias, and poor outcome. Compound genetic mutations leading to complex phenotype in the setting of cardiomyopathies represent an important challenge in clinical practice, and genetic tests allow risk stratification and personalized clinical management of patients. We report a case of a 50-year-old woman with congestive heart failure characterized by dilated cardiomyopathy, diffuse coronary disease, complete atrioventricular block, and missense mutations in cardiac myosin-binding protein C (MYBPC3) and myopalladin (MYPN). We discuss the plausible role of genetic profile in phenotype determination.

Role of Subclinical Iatrogenic Hyperthyroidism in the Setting of Heart Disease and Arrhythmic Burden.

BACKGROUND: Subclinical hyperthyroidism is defined by a subnormal serum thyroidstimulating hormone (TSH) level with normal free thyroxine (FT4) and free triiodothyronine (FT3) levels. Its prevalence varies from 0.6% to 16% in the elderly and can increase to 20% in patients receiving thyroid hormone replacement therapy. Thyroid disease and/or replacement therapy are frequently associated with cardiovascular involvement. CASES PRESENTATION: We report three clinical cases of patients with initial subclinical hyperthyroidism and cardiological manifestations, including supraventricular and ventricular extrasystoles, prolapse of the mitral valve with severe regurgitation, higher mean heart rate and deterioration of the arrhythmias on arrhythmogenic dysplasia substrate. CONCLUSION: We discuss the role of appropriate and early correction of thyroid dysfunction in improving cardiological manifestations.

Prehospital ECG transmission results in shorter door-to-wire time for STEMI patients in a remote mountainous region.

BACKGROUND: Pre-hospital triage with ECG-transmission may reduce time to reperfusion in patients with ST-elevation acute myocardial infarction (STEMI). Less, however, is known on potential benefit of ECG-transmission triage in mountain areas, with complex orography. METHODS: Patients admitted for STEMI and primary coronary angioplasty (pPCI) in a mountain area served by a single cathlab and triaged with ECG-transmission were enrolled in the study and compared with controls: patients' demographics and time to coronary wire were recorded. RESULTS: Forty-seven consecutive patients were enrolled in the study: 23 patients following ECG transmission and 24 STEMI patients who presented directly to the Emergency Department. At multivariable regression analysis, pre-hospital ECG-transmission electrocardiogram was an independent predictor of shorter time-to-wire (beta -0.34, p < 0.05). In case of transport times >30 min, ECG-transmission triage achieved time-to-wire times 20% shorter. Excluding unreducible transport time, avoidable delay was reduced by 38% in the whole population, by 48% in case of peripheral areas (transport time > 30 min from cathlab) and elderly (>80 years) patients (p < 0.05 in all cases). CONCLUSIONS: Pre-hospital triage with ECG-transmission is associated with shorter ischemic time even in mountain areas with a complex orography profile. The benefit is greater in elderly patients and remote areas.

Inappropriate shock and percutaneous cardiac intervention: A lesson to learn in the cath lab.

Coronary disease is a common condition in patients affected by heart failure with severely reduced ejection fraction (HFrEF). This condition represents an indication for implantable cardioverter defibrillator (ICD) in order to reduce the risk of sudden death related to arrhythmias. Nevertheless, inappropriate shocks are associated with worse quality of life, hospitalization, and death. We present the case of an inappropriate shock related to percutaneous coronary intervention during the insertion and advancement of the guidewire into the left anterior descending artery (LAD) in a patient with an ICD. Physicians' awareness about the clinical implication of noise arising during a coronary procedure is very important in patients with an ICD or pacemaker, to avoid inappropriate shock or pacing inhibition and to raise the possibility of lead implantation in or helix protrusion into the coronary lumen.

Long QT syndrome in chromosome 7q35q36.3 deletion involving KCNH2 gene: Warning for chlorpheniramine prescription.

BACKGROUND: The deletion of the distal 7q region is a rare chromosomal syndrome characterized by wide phenotypic manifestations including growth and psychomotor delay, facial dysmorphisms, and genitourinary malformations. METHODS: We describe a 6-year-old child with a 12-Mb deletion of the region 7q35q36.3. RESULTS: Among the deleted genes, two genes have cardiac implications: PRKAG2 (OMIM #602743), associated with hypertrophic cardiomyopathy, cardiac conduction disease, and sudden death, and KCNH2 (OMIM #152427), coding for a cardiac potassium channel involved in long QT syndrome, unmasked by the chlorpheniramine treatment. At same time, the SHH gene (OMIM #600725), encoding sonic hedgehog, a secreted protein that is involved in the embryonic development, is deleted. CONCLUSION: Our report underlines potential cardiac complications linked to the common pharmacological treatment in this rare multiorgan and proteiform disease.

Electrical Remodeling of Ventricular Repolarization Abnormality after Treatment in Pheochromocytoma: U Wave Finding in a Retrospective Analysis.

Background: Pheochromocytoma is a rare neuroendocrine tumor, clinically characterized by high blood pressure, palpitations, and headache. It is often associated with abnormalities of the ventricular repolarization phase; the dispersion of ventricular repolarization is the basis for ventricular arrhythmias (torsion de point, ventricular tachycardia or ventricular fibrillation). Objectives: Analysis of abnormal ventricular repolarization focused on the presence and amount of U wave in patients affected by pheochromocytoma and its modification after surgery. Materials and Methods: We reviewed pathology records of 722 patients admitted for adrenal nodule or suspected chromaffin-cell tumor and identified 39 patients affected by pheochromocytoma. Metanephrine, normetanephrine, and 3-methoxytyramine have been assessed by determining concentrations in 24-hour urine collection. Standard 12-lead electrocardiogram records have been reviewed with analysis of heart rate, P wave, PR interval, QRS duration, QTc, and U wave. Then we selected and compared 22 patients of 39 affected by pheochromocytoma, with both clinical and electrocardiographic data before and after surgery. Results: In our cohort of 39 patients affected by pheochromocytoma, we found U wave in ECG, before treatment, in 82.8 percent of patients, while only 37.0 percent after treatment (p<0.001) and we observed a statistically significant correlation between this wave and the urinary metanephrine. After surgery, in the selected 22 patients, we observed a clear significant reduction in systemic blood pressure, fasting glucose, metanephrine, normetanephrine, and 3-methoxytyramine. We found a significant reduction of U wave presence and leads involved in these patients after surgery (90.9% versus 9%). We observed a linear correlation between the amount of U waves in 12-lead electrocardiogram and metanephrine (r2=0.333, p=0.015), 3-methoxytyramine levels (r2=0.458, p=0.006), and tumor size (r2=0.429, p=0.003). Conclusions: In our retrospective analysis, patients affected by pheochromocytoma presented U wave in electrocardiogram. The presence and amount of U wave were associated with the metanephrine levels and the tumor size with significant reduction after surgical removal.

Sudden death in mild hypertrophic cardiomyopathy with compound DSG2/DSC2/MYH6 mutations: Revisiting phenotype after genetic assessment in a master runner athlete.

Cardiomyopathies represent a well-known cause of heart failure and sudden death. Although cardiomyopathies are generally categorized in distinct nosographic entities, characterized by single gene-to-disease causal relationships, recently, oligogenic mutations have also been associated to relevant cardiac clinical features. We report the case of a master athlete carrying trigenic mutations in desmoglein-2 (DSG2), desmocollin-2 (DSC2) and heavy chain myosin 6 (MYH6), which determine a mild hypertrophic phenotype associated both to ventricular tachyarrhythmias and atrio-ventricular block. We discuss the differential diagnosis and prognostic approach in patient affected by complex cardiomyopathy phenotype, along with the importance of sport restriction and sudden death prevention.

Timing of clopidogrel loading dose on peripheral blood endothelial progenitor cells, SDF-1α and neointimal hyperplasia in carotid stenting.

BACKGROUND: Carotid stenting stimulates intimal proliferation through platelet and stem cell activation. OBJECTIVE: The aim of this study is to evaluate whether the administration before or after carotid stenting of clopidogrel loading dose may play a role on circulating endothelial progenitor cells, stromal cell-derived factor-1α (SDF-1α) and neointimal hyperplasia. METHODS: We recruited 13 patients (aged 74.52±7.23) with indication of carotid revascularization and in therapy with salicylic acid and statin. We blindly randomized them in two groups: pre-carotid angioplasty with stent (Pre-CAS group) receiving 300 mg of clopidogrel before stenting, and post-carotid angioplasty with stent (Post-CAS group) receiving 300 mg after stenting. At the admission, we valued endothelial progenitor cells, SDF-1α and prospectively we repeated blood samples and measured intima-media thickness to estimate neointimal hyperplasia on the stent at 3, 6 and 12 months. RESULTS: In the days following the CAS, we found a lower, statistically not significant, trend of endothelial progenitor cells in Pre-CAS group. The SDF-1α concentration tended to be lower at baseline in the pre-CAS group than in the post-CAS group and it did not show an increase in the observed time. On the contrary, in the Post-CAS group we observed a peak at six hours with a significant reduction (p < 0.001) at one day after stenting.The intima-media thickness was significantly lower in the Pre-CAS group than the Post-CAS group both at six months and 12 months after stenting. CONCLUSIONS: Pre-stenting clopidogrel loading dose leaded to short-time modification of endothelial progenitor cells and platelets and to long-term a minor neointimal hyperplasia.

Sudden cardiac death in J wave syndrome with short QT associated to a novel mutation in Nav 1.8 coding gene SCN10A: First case report for a possible pharmacogenomic role.

INTRODUCTION: Sudden cardiac death is an important cause of mortality in the general population. It represents an important challenge for clinicians, often being the only symptom of a broad spectrum of cardiac pathologies and inherited heart conditions. Early repolarization syndrome and Brugada syndrome are part of the wider "J-wave" syndrome, which may also include the short QT syndrome as a third factor of an ionic channel imbalance in the arrhythmogenic landscape. CASE PRESENTATION: We describe the case of a woman struck down by sudden cardiac death, with short QT and early repolarization, in which we found an extremely rare and putatively pathogenic heterozygous variant in the SCN10A gene. Variants involving SCN10A, which encodes a voltage-gated sodium channel, were already associated with alterations of cardiac conduction parameters and the cardiac rhythm disorder, thereby influencing the cardiac physiology and predisposing to arrhythmia. CONCLUSION: We underline the role of genetic predisposition to sudden cardiac death and, for the first time, suggest a possible environmental effect, such as a pharmacological therapy in the setting of sudden death, with the purpose to increase awareness in clinical practice.

Role of the APOE polymorphism in carotid and lower limb revascularization: A prospective study from Southern Italy.

BACKGROUND: Atherosclerosis is a complex multifactorial disease and the apolipoprotein E (APOE) polymorphism has been associated to vascular complications of atherosclerosis. OBJECTIVES: To investigate the relationship between the APOE genotypes and advanced peripheral vascular disease. MATERIALS AND METHODS: 258 consecutive patients (201 males and 57 females, mean age 70.83 ± 7.89 years) with severe PVD were enrolled in a 42-months longitudinal study (mean 31.65 ± 21.11 months) for major adverse cardiovascular events. At follow-up genotypes of the APOE polymorphism were investigated in blinded fashion. RESULTS: As compared with ε3/ε3, in ε4-carriers a significant higher incidence of major adverse cardiovascular events (35.58% vs. 20.79%; p = 0.025) and total peripheral revascularization (22.64% vs. 5.06%; p < 0.001) was observed. Prospective analysis, showed that ε4-carriers have an increased hazard ratio for major adverse cardiovascular events (adjusted HR 1.829, 95% CI 1.017-3.287; p = 0.044) and total peripheral revascularization (adjusted HR = 5.916, 95% CI 2.405-14.554, p <0.001). CONCLUSIONS: The ε4 allele seems to be risk factor for major adverse cardiovascular events, and in particular for total peripheral revascularization in patients with advanced atherosclerotic vascular disease.

Serum uric acid as a prognostic marker in the setting of advanced vascular disease: a prospective study in the elderly.

BACKGROUND: Many epidemiological studies analyze the relationship between hyperuricemia and cardiovascular outcomes. This observational prospective study investigates the association of serum uric acid (SUA) levels with adverse cardiovascular events and deaths in an elderly population affected by advanced atherosclerosis. METHODS: Two hundred and seventy six elderly patients affected by advanced atherosclerosis (217 males and 59 females; aged 71.2 ± 7.8 years) were included. All patients were assessed for history of cardiovascular disease, cancer, obesity and traditional risk factors. Patients were followed for approximately 31 ± 11 months. Major events were recorded during follow-up, defined as myocardial infarction, cerebral ischemia, myocardial and/or peripheral revascularization and death. RESULTS: Mean SUA level was 5.47 ± 1.43 mg/dL; then we further divided the population in two groups, according to the median value (5.36 mg/dL). During a median follow up of 31 months (5 to 49 months), 66 cardiovascular events, 9 fatal cardiovascular events and 14 cancer-related deaths have occurred. The patients with increased SUA level presented a higher significant incidence of total cardiovascular events (HR: 1.867, P = 0.014, 95% CI: 1.134-3.074). The same patients showed a significant increased risk of cancer-related death (HR: 4.335, P = 0.025, 95% CI: 1.204-15.606). CONCLUSIONS: Increased SUA levels are independently and significantly associated with risk of cardiovascular events and cancer related death in a population of mainly elderly patients affected by peripheral vasculopathy.

Improvement of migraine after patent foramen ovale percutaneous closure in patients with subclinical brain lesions: a case-control study.

OBJECTIVES: We sought to evaluate the benefits on frequency and severity of migraine recurrence after patent foramen ovale (PFO) closure in patients with subclinical brain lesions at magnetic resonance imaging (MRI). BACKGROUND: Migraine improvement has been reported after PFO closure in patients with cerebrovascular symptomatic events. Subclinical brain MRI lesions are detectable in patients with PFO and in migraineurs. METHODS: A total of 82 patients with moderate/severe migraine, PFO, large right-to-left shunt, and subclinical brain MRI lesions were prospectively examined for a 6-month period. Patients were subdivided into closure (n = 53) and control (n = 29) group according to their consent to undergo percutaneous PFO closure. In controls, therapy for migraine was optimized. Six-month frequency and severity of migraine recurrence were compared with baseline. RESULTS: The number of total attacks decreased more in the closure group (32 +/- 9 to 7 +/- 7, p < 0.001) than in the control group (36 +/- 13 to 30 +/- 21, p = NS) (p < 0.001). A significant reduction in disabling attacks was observed only in the closure group (20 +/- 12 to 2 +/- 2, p < 0.001; controls: 15 +/- 12 to 12 +/- 12, p = NS). Migraine disappeared in 34% of the closure group patients and 7% of controls (p = 0.007); >50% reduction of attacks was reported by 87% and 21%, respectively (p < 0.001). Disabling attacks disappeared in 53% of closure group patients and 7% of controls (p < 0.001); >50% reduction occurred in 89% and 17%, respectively (p < 0.001). CONCLUSIONS: In migraineurs with a large PFO and subclinical brain MRI lesions, a significant reduction in frequency and severity of migraine recurrence can be obtained by PFO closure when compared with frequency and severity in controls.

Double rhythm in double heart.

We describe the case of a patient with heterotopic transplantation, sinus rhythm originating from the donor heart, ventricular fibrillation of the native heart and right severe decompensation. The double rhythm was easily detected with a surface ECG and the transthoracic echocardiogram, both performed in the left conventional and in the right modified mode. The patient was successfully treated with direct current shock with quick restoration of native heart synchronization and clinical relief of symptoms.

Inaccuracy of dipyridamole echocardiography or scintigraphy for the diagnosis of coronary artery disease in patients with both left bundle branch block and left ventricular dysfunction.

Non-invasive diagnosis of coronary artery disease (CAD) in patients with left ventricular (LV) dysfunction and left bundle branch block (LBBB) remains challenging, and there is no consensus on the role of myocardial sesta-MIBI perfusion scintigraphy with pharmacological stress (dip-MIBI) or dipiridamole echocardiography (dip-ECHO). We thus performed a prospective study to test the diagnostic accuracy of such non-invasive tests. 27 consecutive patients with both LV dysfunction and LBBB undergoing diagnostic work-up for CAD were studied simultaneously with dip-ECHO and dip-MIBI. The sensitivity for CAD for dip-ECHO and dip-MIBI was respectively 42% and 67%, with specificity 93% and 53%, and likelihood ratio (LR)-positive 6.3 and LR-negative 0.6 for both. Given the low accuracy of both dip-ECHO and dip-MIBI in detecting CAD in patients with concomitant LV dysfunction and LBBB, coronary angiography should be performed as the default diagnostic strategy in such patients.

[Cardiac metastasis of poorly differentiated adenocarcinoma of unknown primary site]. / Metastasi cardiache di adenocarcinoma poco differenziato a sede primitiva occulta.

The finding of intracardiac masses is very uncommon. In this patient the early clinical picture was characterized by neurologic signs and symptoms as mild forgetfulness, blurred vision, a sensation of imbalance, anorexia, weight loss. Brain magnetic resonance imaging showed multiple metastatic lesions, computed tomography of the chest, abdomen and pelvis showed intraatrial masses and whole body nuclear scanning evidenced bone lesion. It was not possible to find the primary tumor by other instrumental or laboratory exams. Transesophageal echocardiography showed a mass originating from interatrial septum, with atrial invasion and risk of embolization from the left atrium. The patient was transferred to the operating room for cardiac surgery, the mass at risk for embolization was resected and the specimen consisted of fibrous and fibrino-necrotic tissue infiltrated by poorly differentiated adenocarcinoma. The patient received brain and bone radiotherapy and chemotherapy with cisplatin and vinorelbin.