Coronary microvascular dysfunction affects left ventricular global longitudinal strain response to dipyridamole stress echocardiography: a pilot study.

The aim is to investigate, by means of speckle tracking echocardiography, left ventricular (LV) contractile function at rest and during dipyridamole stress in patients with coronary microvascular dysfunction (CMD). 59 patients (39% women, mean age 65.6 ± 6.1 years) with history of chest pain and without obstructive coronary artery disease (CAD) underwent dipyridamole stress echocardiography. Coronary flow was assessed in the left anterior descending coronary artery. Coronary flow reserve (CFR) was determined as the ratio of hyperaemic to baseline diastolic coronary flow velocity. CMD was defined as CFR < 2. Global longitudinal strain (GLS) was measured at rest and at peak dose. Nineteen patients (32%) among the overall population showed CMD. Baseline GLS was significantly lower in patients with CMD (- 16.8 ± 2.7 vs. - 19.1 ± 3.1, p < 0.01). A different contractile response to dipyridamole infusion was observed between the two groups: GLS significantly increased up to peak dose in patients without CMD (from - 19.1 ± 3.1 to - 20.2 ± 3.1, p < 0.01), and significantly decreased in patients with CMD (from - 16.8 ± 2.7 to - 15.8 ± 2.7, p < 0.01). There was a significant inverse correlation between CFR and ∆GLS (r = - 0.82, p < 0.01). Rest GLS and GLS response to dipyridamole stress are markedly impaired among patients with chest pain syndrome, non-obstructive CAD and CMD, reflecting subclinical LV systolic dysfunction and lack of LV contractile reserve due to underlying myocardial ischemia.

The effects of lockdown-induced air quality changes on the results of cardiac functional stress testing in coronary artery disease and heart failure patients.

In vulnerable subjects, the increase in air pollution worsens the signs of myocardial ischemia. Lockdown during COVID-19 pandemics substantially cleaned the air. The objective of this is to assess the effects of air cleaning due to lockdown on stress echocardiography (SE) results. We enrolled 19 patients with chronic coronary artery disease and/or heart failure referred to SE (semi-supine bicycle exercise, n = 8, or dipyridamole, n = 11). Before and soon after lockdown, we assessed regional wall motion abnormalities (abnormal value: worsening of ≥ 2 segments), B-lines (a sign of pulmonary congestion, 4-site simplified scan, abnormal value ≥ 2), and coronary flow velocity reserve in left anterior descending artery (CFVR, abnormal value < 2.0). Local air quality indicators (same day of SE) of fine particulate matter (PM2.5) and nitrogen dioxide (NO2) were obtained from publicly available data sets of the regional authority of environmental protection. After lockdown, NO2 concentration decreased from 19 ± 10 to 10 ± 4 µg/m3 (p = 0.006). After lockdown, abnormal responses remained unchanged for ischemia (21% vs 16%, p = ns) and decreased for B-lines (42% vs 5%, p = 0.008) and CFVR (84 vs 42%, p = 0.007). Changes in coronary flow velocity reserve (CFVR) were correlated to same-day variations in NO2 (r = -0.578, p = 0.010) and preceding 30-day changes in PM2.5 (r = -0.518, p = 0.023). After lockdown, air cleaning was associated with a beneficial effect on coronary small vessel dysfunction and alveolar-capillary barrier distress mirrored by improvement of CFVR and B-lines during SE in vulnerable patients. ClinicalTrials.gov Identifier: NCT 030.49995.

Multimodality imaging in COVID-19 patients: A key role from diagnosis to prognosis.

The integrated clinical, laboratory and ultrasound approach is essential for the diagnosis, evaluation and monitoring of the patient's therapy in coronavirus disease 2019 pneumonia. The ideal imaging approach in this context is not yet well defined. Chest X-ray is characterized by low sensitivity in identifying earlier lung changes. The "bedside" pulmonary ultrasound has an undeniable series of advantages in the patient at high infectious risk and can provide incremental data in the respiratory intensive care for the serial control of the individual patient as well as for the home delivery of the stabilized subjects. Pulmonary computed tomography shows high sensitivity but should not be routinely performed in all patients, because in the first 48 h it can be absolutely negative and in the late phase the imaging findings may not change the therapeutic approach. Echocardiography should be limited to patients with hemodynamic instability to assess ventricular function and pulmonary pressures.

The Pharmacological Approach to Oncologic Patients with Acute Coronary Syndrome.

Among acute coronary syndrome (ACS) patients, 15% have concomitant cancer, especially in the first 6 months after their diagnosis, as well as in advanced metastatic stages. Lung, gastric, and pancreatic cancers are the most frequent malignancies associated with ACS. Chemotherapy and radiotherapy exert prothrombotic, vasospastic, and proinflammatory actions. The management of cancer patients with ACS is quite challenging: percutaneous revascularization is often underused, and antiplatelet and anticoagulant pharmacological therapy should be individually tailored to the thrombotic risk and to the bleeding complications. Sometimes oncological patients also show different degrees of thrombocytopenia, which further complicates the pharmacological strategies. The aim of this review is to summarize the current evidence regarding the treatment of ACS in cancer patients and to suggest the optimal management and therapy to reduce the risk of adverse coronary events after ACS in this high-risk population.

The K219T-Lamin mutation induces conduction defects through epigenetic inhibition of SCN5A in human cardiac laminopathy.

Mutations in LMNA, which encodes the nuclear proteins Lamin A/C, can cause cardiomyopathy and conduction disorders. Here, we employ induced pluripotent stem cells (iPSCs) generated from human cells carrying heterozygous K219T mutation on LMNA to develop a disease model. Cardiomyocytes differentiated from these iPSCs, and which thus carry K219T-LMNA, have altered action potential, reduced peak sodium current and diminished conduction velocity. Moreover, they have significantly downregulated Nav1.5 channel expression and increased binding of Lamin A/C to the promoter of SCN5A, the channel's gene. Coherently, binding of the Polycomb Repressive Complex 2 (PRC2) protein SUZ12 and deposition of the repressive histone mark H3K27me3 are increased at SCN5A. CRISPR/Cas9-mediated correction of the mutation re-establishes sodium current density and SCN5A expression. Thus, K219T-LMNA cooperates with PRC2 in downregulating SCN5A, leading to decreased sodium current density and slower conduction velocity. This mechanism may underlie the conduction abnormalities associated with LMNA-cardiomyopathy.

Echocardiography in Athletes in Primary Prevention of Sudden Death.

Echocardiography is a noninvasive imaging technique useful to provide clinical data regarding physiological adaptations of athlete's heart. Echocardiographic characteristics may be helpful for the clinicians to identify structural cardiac disease, responsible of sudden death during sport activities. The application of echocardiography in preparticipation screening might be essential: it shows high sensitivity and specificity for identification of structural cardiac disease and it is the first-line imagining technique for primary prevention of SCD in athletes. Moreover, new echocardiographic techniques distinguish extreme sport cardiac remodeling from beginning state of cardiomyopathy, as hypertrophic or dilated cardiomyopathy and arrhythmogenic right ventricle dysplasia. The aim of this paper is to review the scientific literature and the clinical knowledge about athlete's heart and main structural heart disease and to describe the rule of echocardiography in primary prevention of SCD in athletes.

Effectiveness and Safety of Transcatheter Aortic Valve Implantation in Patients With Pure Aortic Regurgitation and Advanced Heart Failure.

Results of transcatheter aortic valve implantation (TAVI) for treatment of severe noncalcific isolated aortic regurgitation (AR) complicated by advanced heart failure or cardiogenic shock has been previously reported only in isolated case reports. Current self-expanding transcatheter aortic valves are designed to treat aortic valve stenosis, and have also been implanted in cases of severe AR due to degenerated bioprosthesis and in very few cases of native aortic valves. We report 13 consecutive inoperable patients with noncalcific, pure AR, and advanced heart failure treated with emergency percutaneous transfemoral implantation with self-expandable CoreValves at our institution between July 2012 and September 2017. The immediate and long-term clinical outcome was prospectively assessed according to the Valve Academic Research Consortium-2 criteria for device success and safety. All but 3 patients had previous surgery of the aortic root, including 2 implants of Heart Mate-II left ventricle assist device; none had surgical aortic bioprosthesis at the time of the TAVI. Valve implantation was successful in 12 of 13 patients (92%) and 1 patient required a second unplanned valve procedure within 18 hours. Oversizing the prosthesis by approximately 15% yielded better results with 1 valve. Two patients with left ventricle assist device died within 30 days of TAVI. All patients who survived to hospital discharge had none or just mild residual AR, improved their cardiac function, and survived at long-term without recurrence of clinical events. In conclusion, implanting self-expandable transcatheter valves in patients pure AR in this small study was safe and effective, and represented an important option for inoperable patients with noncalcific severe AR.

Everolimus-Eluting Bioresorbable Vascular Scaffold System in the Treatment of Cardiac Allograft Vasculopathy: the CART (Cardiac Allograft Reparative Therapy) Prospective Multicenter Pilot Study.

Cardiac allograft vasculopathy (CAV) is a form of accelerated atherosclerosis, which represents the leading cause of late morbidity and mortality after heart transplantation. The recent bioresorbable vascular scaffold (BVS) technology represents a potential novel therapeutic tool, in the context of CAV, by allowing transient scaffolding and concomitant vessel healing. Eligible subjects will be treated by using the Absorb Everolimus-Eluting BVS (Abbott Vascular, Santa Clara, CA, USA), and evaluated at pre-determined time points, up to 3 years since the index procedure. Both clinical and imaging data will be collected in dedicated case report forms (CRF). All imaging data will be analyzed in an independent core laboratory. The primary aim of the study is to evaluate the angiographic performance at 1 year of second-generation Absorb BVS, in heart transplant recipients affected by CAV.

Disseminated Mycobacterium avium complex disease in a patient with left ventricular assist device (Heart Mate II).

Although disseminated Mycobacterium avium complex disease occurs mainly in immunocompromised hosts, especially HIV-infected patients in the last stage of the disease (AIDS), this condition is still rare in immunocompetent subjects. We report the case of a Caucasian man who received a left ventricular assist device two years before as a bridge to heart transplantation, that began to present signs and symptoms of mycobacterial infection. The diagnostic work-up we performed showed the presence of Mycobacterium intracellulare in lungs and both peripherical and bone marrow blood. Although evaluated, we found no abnormalities in the patient's immune system that can be related to mycobacterial infection. The beginning of a specific therapy made the patient slowly improve and further nuclear medicine assay (PET-TC) showed a good reduction in radio-labelled drug captation.

[Thalamo-mesencephalic aspergillus abscess in a heart transplant subject: a case report and literature review]. / Ascesso aspergillare talamo-mesencefalico in un soggetto sottoposto a trapianto cardiaco: caso clinico e revisione della letteratura.

Cerebral aspergillosis is a rare and highly fatal infection that mainly affects immunocompromised patients. We report on a case of a heart transplanted Caucasian man, who arrived at our hospital because of the onset of diplopy. We performed a broad diagnostic work-up: the brain MRI showed a single ring-enhancing thalamo-mesencephalic area suggestive of abscess lesion; cerebrospinal fluid (CSF) analysis disclosed galactomannan and beta-D-glucan antigens. Thus the antifungal therapy was immediately started. We decided to discontinue the therapy 16 months later because of severe hepatic toxicity, given that the patient was persistently asymptomatic, brain imaging showed a progressive resolution of the abscess area and CSF antigen analysis was persistently negative. The follow-up at three months was unchanged.

Doubly heterozygous LMNA and TTN mutations revealed by exome sequencing in a severe form of dilated cardiomyopathy.

Familial dilated cardiomyopathy (DCM) is a heterogeneous disease; although 30 disease genes have been discovered, they explain only no more than half of all cases; in addition, the causes of intra-familial variability in DCM have remained largely unknown. In this study, we exploited the use of whole-exome sequencing (WES) to investigate the causes of clinical variability in an extended family with 14 affected subjects, four of whom showed particular severe manifestations of cardiomyopathy requiring heart transplantation in early adulthood. This analysis, followed by confirmative conventional sequencing, identified the mutation p.K219T in the lamin A/C gene in all 14 affected patients. An additional variant in the gene for titin, p.L4855F, was identified in the severely affected patients. The age for heart transplantation was substantially less for LMNA:p.K219T/TTN:p.L4855F double heterozygotes than that for LMNA:p.K219T single heterozygotes. Myocardial specimens of doubly heterozygote individuals showed increased nuclear length, sarcomeric disorganization, and myonuclear clustering compared with samples from single heterozygotes. In conclusion, our results show that WES can be used for the identification of causal and modifier variants in families with variable manifestations of DCM. In addition, they not only indicate that LMNA and TTN mutational status may be useful in this family for risk stratification in individuals at risk for DCM but also suggest titin as a modifier for DCM.

Analysis of the 3'UTR of the prostaglandin synthetase-2 (PTGS-2/COX-2) gene in non-melanoma skin cancer after organ transplantation.

To define the potential involvement of polymorphisms in the 3'untranslated region (3'UTR) of the prostaglandin synthetase-2 (PTGS-2) gene to non-melanoma skin cancer (NMSC) predisposition after transplantation, we screened for genetic variant, relevant parts of this region. It contains binding sites for trans-acting factors, an alternative polyadenylation site and putative target sequences for miRNAs. Variant +8473T>C did not appear to play a functional role in the regulation of gene expression in human keratinocyte-transfected cells. In addition to the well-known +8473T>C, we identified four polymorphisms: +8293G>C, +10259T>G, +10267G>A and +10335G>A. No allele frequency differences were observed between cases and controls neither for +8473T>C nor for any of the identified polymorphisms, suggesting that polymorphisms in the 3'UTR of the PTGS2 gene are rare and unlikely to represent risk factor for NMSC after transplantation.

Myocardial protection in heart transplantation using blood cardioplegia: 12-year outcome of a prospective randomized trial.

BACKGROUND: Blood cardioplegia yields a lower prevalence of right heart failure, arrhythmias, and myocardial ischemia early after heart transplantation (HTx). Because depolarizing (high [K(+)]) cardioplegic solutions may alledgedly cause endothelial damage, the 12-year outcome of a prospective randomized trial was reviewed. METHODS: Between January 1997 and March 1998, 47 consecutive patients received crystalloid (Group 1, n = 27) or blood cardioplegia (Group 2, n = 20). The groups were similarly matched: recipient age (54 ± 11 vs 55 ± 7 years, p = 0.9), sex (89% vs 90% males, p = 0.9), diagnosis (63% vs 65% dilated cardiomyopathy, p = 0.8), elevated (>4 WU) pulmonary vascular resistance (30% vs 30%, p = 0.9), prior operations (22% vs 30%, p = 0.5), urgent HTx (7% vs 20%, p = 0.2), donor age (32 ± 11 vs 31 ± 13 years, p = 0.7), donor sex (78% vs 70% males, p = 0.5), donor cause of death (33% vs 40% vascular, p = 0.5), and global myocardial ischemia (176 ± 51 vs 180 ± 58 minutes p = 0.5). Hemodynamically unstable donors were more prevalent in Group 2 (15% vs 45%, p = 0.02). The 45 hospital survivors underwent yearly echocardiography, coronary angiography, and coronary intravascular ultrasound (IVUS) imaging during follow-up. RESULTS: During follow-up (10.4 ± 5.2, range, 0.9-12.7 years), Groups 1 and 2 had comparable mortality (46% vs 42%, p = 0.7) and cause of death (chronic rejection: 50% vs 50%; neoplasia: 33% vs 25%, p = 0.8). Survival at 12 years was 50% ± 12% vs 52% ± 11% (p = 0.9). Follow-up echocardiogram showed similar mean left ventricular ejection fraction (LVEF; 47% ± 12% vs 49% ± 11%, p = 0.7) and prevalence of LVEF < 35% (21% vs 18%, p = 0.8). Prevalence of chronic rejection was comparable (42% vs 32%, p = 0.1), yet severe allograft vasculopathy (International Society for Heart and Lung Transplantation cardiac allograft vasculopathy 3) was more prevalent in Group 1 (64% vs 17%, p = 0.04). Freedom from chronic rejection was higher in Group 2 (44% ± 15% vs 63% ± 13%), albeit not significantly (p = 0.5). A trend toward greater prevalence of intimal disease at IVUS (thickness > 0.5 mm) in the proximal and distal left anterior descending artery (67% vs 40%; 58% vs 45%) and higher number of percutaneous coronary interventions (2.7 ± 0.5 vs 1.8 ± 0.3, p = 0.3) was noted in Group 1. CONCLUSIONS: Use of blood cardioplegia is safe and results in comparable survival and prevalence of adverse events late after HTx. The trend towards greater freedom from chronic rejection and more limited extent of coronary artery disease in grafts protected with blood cardioplegia awaits confirmation.

Impact of donor quality on outcome of heart transplantation.

OBJECTIVE: Over the last few years, there have been changes in both donor and recipient profiles in heart transplantation. Encouraging clinical outcome of marginal donors in candidates older than 60 years of age led us to allocate suboptimal donors for younger recipients as well. We reviewed our experience retrospectively so as to assess the impact of donor quality on heart transplantation. METHODS: Among 181 patients who underwent heart transplantation between January 2000 and February 2009, there were 75 patients (41%) aged 61-70 years and 106 patients (59%) ranging in age between 18 and 60 years. According to the recipient's age, they were classified into four groups. The younger recipients (106 patients) had either optimal donors (70 patients, group 1) or marginal donors (36 patients, group 2). The older recipients (75 patients) had either marginal grafts (64 patients, group 3) or optimal grafts (11 patients, group 4). Sex distribution, cause of end-stage heart failure, preoperative pulmonary hypertension, pre-heart-transplantation clinical status or mean follow-up duration did not show any statistically significant difference among the four groups. RESULTS: Overall, the 9-year actuarial survival rate was 78%±1%. The 30 days and 9-year actuarial survival rates were 94%±2% and 80%±1% in group 1; 86%±5% and 55%±12% in group 2; 90%±4% and 73%±7% in group 3; 99%±1% and 82%±7% in group 4 (P=0.07). Comparison among the four groups did not show any statistical difference in terms of freedom from graft failure (P=0.3), right ventricular failure (P=0.3), acute rejection (P=0.2), chronic rejection (P=0.2), neoplasia (P=0.5) and chronic renal failure (P=0.2). Older recipients of marginal donors (group 3) had slightly higher prevalence of permanent pacemaker implants: eight permanent pacemakers versus two in group 2, and none in group 1 and group 4 (P=0.4). CONCLUSIONS: Our results suggest that extended donor acceptance criteria may not compromise clinical outcome after heart transplantation. Further follow-up is warranted.

Incidence and clinical predictors of a subsequent nonmelanoma skin cancer in solid organ transplant recipients with a first nonmelanoma skin cancer: a multicenter cohort study.

OBJECTIVE: To compare the long-term risk of primary nonmelanoma skin cancer (NMSC) and the risk of subsequent NMSC in kidney and heart transplant recipients. DESIGN: Partially retrospective cohort study. SETTING: Two Italian transplantation centers. PATIENTS: The study included 1934 patients: 1476 renal transplant recipients and 458 heart transplant recipients. MAIN OUTCOME MEASURES: Cumulative incidences and risk factors of the first and subsequent NMSCs. RESULTS: Two hundred patients developed a first NMSC after a median follow-up of 6.8 years after transplantation. The 3-year risk of the primary NMSC was 2.1%. Of the 200 patients with a primary NMSC, 91 (45.5%) had a second NMSC after a median follow-up after the first NMSC of 1.4 years (range, 3 months to 10 years). The 3-year risk of a second NMSC was 32.2%, and it was 49 times higher than that in patients with no previous NMSC. In a Cox proportional hazards regression model, age older than 50 years at the time of transplantation and male sex were significantly related to the first NMSC. Occurrence of the subsequent NMSC was not related to any risk factor considered, including sex, age at transplantation, type of transplanted organ, type of immunosuppressive therapy, histologic type of the first NMSC, and time since diagnosis of the first NMSC. Histologic type of the first NMSC strongly predicted the type of the subsequent NMSC. CONCLUSIONS: Development of a first NMSC confers a high risk of a subsequent NMSC in transplant recipients. Intensive long-term dermatologic follow-up of these patients is advisable.

Incidence and clinical predictors of primary opportunistic deep cutaneous mycoses in solid organ transplant recipients: a multicenter cohort study.

BACKGROUND: Primary opportunistic deep cutaneous fungal infections may cause significant morbidity and mortality in solid organ transplant recipients (OTR), but no data exist about their incidence, timing, and clinical predictors in a long-term follow-up. PATIENTS AND METHODS: A series of 3293 consecutive OTR including 1991 kidney, 929 heart, and 373 liver transplant recipients were enrolled. Patients were regularly followed up since time at transplantation (mean 5.5 yr +/-5.9 SD) and primary opportunistic fungal infections registered. Persons-year at risk (PYs), incidence rates (IR), incidence rate ratios (IRR), and 95% confidence intervals were computed. RESULTS: Twenty-two cases of deep cutaneous mycoses were detected, (IR 1.2 cases per 1000 PYs) after a mean follow-up time since transplantation of 2.5 yr +/- 2.0 SD (median 1.8 yr). Six patients had subsequent systemic involvement and three patients died of systemic dissemination. A higher risk for mycoses was observed in the first two yr after transplantation, (IRR 35.9, p < 0.0001), in renal transplant recipients (IRR 5.1 p = 0.030), and in patients transplanted after the age of 50 (IRR 11.5 p = 0.020). CONCLUSIONS: Primary deep cutaneous opportunistic mycoses in OTR occur mainly in the first two yr after transplantation, in renal transplant recipients, and in older patients.

[Early interventricular septum rupture after systemic thrombolysis in a patient with STEMI]. / Rottura precoce di setto interventricolare dopo trombolisi sistemica nell'infarto miocardico acuto con ST elevation.

Intraventricular septal rupture (ISR) is one of the most dreadful complications during AMI, requiring early diagnosis and urgent surgery. However, medical (90%) and surgical (50%) mortality remain elevated. We report a case of a 59 years old patient with infero-posterior AMI complicated by ISR after thrombolysis. Despite early recognition of this complication by trans-thoracic echocardiography at bedside and prompt surgical intervention the patient died on the second post-surgical day.

Glutathione S-transferase and CYP1A1 gene polymorphisms and non-melanoma skin cancer risk in Italian transplanted patients.

Solid organ transplant recipients are at higher risk of non-melanoma skin cancer (NMSC), especially basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Genetic alterations in the production of detoxifying enzymes such as glutathione S-transferase (GST) and CYP1A1 may enhance this risk. We investigated the frequency of GST genotypes (GSTM1, GSTM3, GSTT1 and GSTP1) and CYP1A1 in 239 transplant recipients: 107 cases with NMSC and 132 controls free from NMSC matched for type of transplanted organ, duration of transplantation, sex and age. Allele GSTP1*A was associated with a higher risk of NMSC [odds ratio (OR) 1.7 (1.1-2.5); P = 0.017]. Homozygosity for allele GSTP1 Val(105) was lower in cases [OR 0.3 (0.1-0.8); P = 0.012], especially in patients with SCC [OR 0.1 (0.0-0.7); P = 0.012]. A higher risk of BCC was found in patients with GSTM1 null/null [null/null versus A + B, OR 3.1 (1.4-6.8); P = 0.003]. Analysis of allelism and interaction between allelic variants showed significant association between combined GSTM1 and CYP1A1 Val(462) genotypes, where individuals homozygous for the risk allele GSTM1 null and carrying also the allele CYP1A1 Val(462), show a higher risk of developing NMSC [OR 4.5 (1.1-21.4); P = 0.03], especially SCC [OR 6.5 (1.4-34.4); P = 0.01]. GSTP1 polymorphisms are associated with both BCC and SCC risk. GSTM1 polymorphisms seem to be involved in BCC risk, while GSTM1 null/null genotype combined with CYP1A1 allele Val(462) are associated with a higher risk for SCC, indicating that allelism and/or interactions between allelic variants at other loci may also influence the risk of NMSC, particularly SCC.