Idiopathic Dilated Cardiomyopathy Research Articles

Association of ADRB1 gene polymorphism with dilated cardiomyopathy

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University Aim To evaluate the Association of rs1801252 polymorphism of the ADRB1 gene with dilated idiopathic cardiomyopathy (DCMP) and myocardial dilation of ischemic origin (DMI). Subjects and methods The study included patients with ICMP and MD IG in the number of 221 people. The average age of the subjects was in the range of 55.30 ± 9.69 years. We divided the patients into 2 groups: the first – patients diagnosed with idiopathic dilatation cardiomyopathy and the second-patients with myocardial dilatation of ichemic origin. The number of patients in the first group was 111, including 99 men (89.2%) and 12 women (10.8%). The average age of patients in this group is 51.73 ± 9.74 years, in men 51.00 ± 8.96 years, in women 57.75 ± 3.71 years. The second group included patients with myocardial dilatation of ischemic origin. Their number is 110 people, including 100 men (91.5%) and 10 women (8.5%). The average age of respondents is 58.68 ± 8.38 years, for men 58.29 ± 8.46 years, for women 62.90 ± 6.29 years. The control group included patients who had no manifestations of cardiovascular diseases. Their number is 121 people (average age 53.6 ± 4.8 years). The patients underwent laboratory and instrumental studies, as well as molecular and genetic studies of the A145G polymorphism of the ADRB1 gene (rs1801252 ). All patients underwent coronary angiography. Based on the anamnesis data and instrumental studies, those patients who could be said to have no risk factors for the development of dilatation of the heart cavities were identified in the first group. And those patients who were reliably diagnosed with CHD were in the second group, that is, dilatation of the heart cavities is due to a previous myocardial infarction, existing angina pectoris. Results In the group with DCMP 70.3% of patients were carriers of the common homozygous A145A genotype, the heterozygous A145G genotype-27.0%, and the rare homozygous G145G genotype-2.7%. In the control group 71.9% of patients were identified as carriers of a homozygous genotype by a common allele, and 25.3% were carriers heterozygous genotype, and homozygous genotype for a rare allele – 2.7%. Statistical analysis showed no achievement of statistical significance level across any of the genotypes. In the group with DM IG, there was no association with the rs1801252 polymorphism of the ADRB1 gene. Conclusion A statistically significant association of rs1801252 of the ADRB1 gene with DCMP was not found. The association of DM IG c rs1801252 could not be confirmed.

Association of ADRB2 gene polymorphism with dilated cardiomyopathy

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University Aim To evaluate the Association of rs1042713 polymorphism of the ADRB2 gene with dilated idiopathic cardiomyopathy (DCMP) and myocardial dilation of ischemic origin (DMI). Subjects and methods The study included patients with ICMP and DMI in the number of 221 people. The average age of the subjects was in the range of 55.30 ± 9.69 years. We divided the patients into 2 groups: the first – patients diagnosed with idiopathic dilatation cardiomyopathy and the second-patients with myocardial dilatation of ichemic origin. The number of patients in the first group was 111, including 99 men (89.2%) and 12 women (10.8%). The average age of patients in this group is 51.73 ± 9.74 years, in men 51.00 ± 8.96 years, in women 57.75 ± 3.71 years. The second group included patients with myocardial dilatation of ischemic origin. Their number is 110 people, including 100 men (91.5%) and 10 women (8.5%). The average age of respondents is 58.68 ± 8.38 years, for men 58.29 ± 8.46 years, for women 62.90 ± 6.29 years. The control group included patients who had no manifestations of cardiovascular diseases. Their number is 121 people (average age 53.6 ± 4.8 years). The patients underwent laboratory and instrumental studies, as well as molecular and genetic studies of the 16 AG polymorphism of the ADRB2 gene (rs1042713). All patients underwent coronary angiography. Based on the anamnesis data and instrumental studies, those patients who could be said to have no risk factors for the development of dilatation of the heart cavities were identified in the first group. And those patients who were reliably diagnosed with CHD were in the second group, that is, dilatation of the heart cavities is due to a previous myocardial infarction, existing angina pectoris. Results In the group with DCMP 10.8% of patients were carriers of the common homozygous 16AA genotype, the heterozygous 16AG genotype-48.6%, and the rare homozygous 16GG genotype-40.5%. In the control group 11.8% of patients were identified as carriers of a homozygous genotype by a common allele, and 47.5% were carriers heterozygous genotype, and homozygous genotype for a rare allele – 40.7%. The analysis non revealed a statistically significant decrease in the frequency of carrying the homozygous 16GG genotype in patients with DCMP compared to the control group of the rs1042713 polymorphism of the ADRB2 gene. In the group with DM IG, there was no association with the rs1042713 polymorphism of the ADRB2 gene. Conclusion A statistically significant association of rs1042713 of the ADRB2 gene with DCMP was not found. The association of DMI c rs1042713 could not be confirmed.

Association of CTLA4 gene polymorphism with dilated cardiomyopathy

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University Aim To evaluate the Association of rs231775 polymorphism of the CTLA4 gene with dilated idiopathic cardiomyopathy (DCMP) and myocardial dilation of ischemic origin (DMI). Subjects and methods The study included patients with ICMP and DMI in the number of 221 people. The average age of the subjects was in the range of 55.30 ± 9.69 years. We divided the patients into 2 groups: the first – patients diagnosed with idiopathic dilatation cardiomyopathy and the second-patients with myocardial dilatation of ichemic origin. The number of patients in the first group was 111, including 99 men (89.2%) and 12 women (10.8%). The average age of patients in this group is 51.73 ± 9.74 years, in men 51.00 ± 8.96 years, in women 57.75 ± 3.71 years. The second group included patients with myocardial dilatation of ischemic origin. Their number is 110 people, including 100 men (91.5%) and 10 women (8.5%). The average age of respondents is 58.68 ± 8.38 years, for men 58.29 ± 8.46 years, for women 62.90 ± 6.29 years. The control group included patients who had no manifestations of cardiovascular diseases. Their number is 121 people (average age 53.6 ± 4.8 years). The patients underwent laboratory and instrumental studies, as well as molecular and genetic studies of the 49A/G polymorphism of the CTLA4 gene (rs231775). All patients underwent coronary angiography. Based on the anamnesis data and instrumental studies, those patients who could be said to have no risk factors for the development of dilatation of the heart cavities were identified in the first group. And those patients who were reliably diagnosed with CHD were in the second group, that is, dilatation of the heart cavities is due to a previous myocardial infarction, existing angina pectoris. Results In the group with DCMP 34.2% of patients were carriers of the common homozygous 49AA genotype, the heterozygous 49AG genotype-48.6%, and the rare homozygous 49GG genotype-17.1%. In the control group 33.5% of patients were identified as carriers of a homozygous genotype by a common allele, and 49.3% were carriers heterozygous genotype, and homozygous genotype for a rare allele – 17.2%. The analysis revealed a statistically non significant increase in the frequency of carrying the homozygous AA genotype in patients with DCMP compared to the control group of the rs231775 polymorphism of the CTLA4 gene. In the group with DMI, there was no association with the rs231775 polymorphism of the CTLA4 gene. Conclusion A statistically significant association of rs231775 of the CTLA4 gene with DCMP was not found. The association of DMI c rs231775 could not be confirmed.

Cardiac retinoic acid levels decline in heart failure.

Although low circulating levels of the vitamin A metabolite, all-trans retinoic acid (ATRA), are associated with increased risk of cardiovascular events and all-cause mortality, few studies have addressed whether cardiac retinoid levels are altered in the failing heart. Here, we showed that proteomic analyses of human and guinea pig heart failure (HF) were consistent with a decline in resident cardiac ATRA. Quantitation of the retinoids in ventricular myocardium by mass spectrometry revealed 32% and 39% ATRA decreases in guinea pig HF and in patients with idiopathic dilated cardiomyopathy (IDCM), respectively, despite ample reserves of cardiac vitamin A. ATRA (2 mg/kg/d) was sufficient to mitigate cardiac remodeling and prevent functional decline in guinea pig HF. Although cardiac ATRA declined in guinea pig HF and human IDCM, levels of certain retinoid metabolic enzymes diverged. Specifically, high expression of the ATRA-catabolizing enzyme, CYP26A1, in human IDCM could dampen prospects for an ATRA-based therapy. Pertinently, a pan-CYP26 inhibitor, talarozole, blunted the impact of phenylephrine on ATRA decline and hypertrophy in neonatal rat ventricular myocytes. Taken together, we submit that low cardiac ATRA attenuates the expression of critical ATRA-dependent gene programs in HF and that strategies to normalize ATRA metabolism, like CYP26 inhibition, may have therapeutic potential.

T1 mapping and conditional survival in paediatric dilated cardiomyopathy with advanced heart failure.

Myocardial fibrosis is associated with adverse events in idiopathic dilated cardiomyopathy. Cardiac MRI with late gadolinium enhancement can detect myocardial fibrosis. We evaluated the conditional survival of children and adolescents based on native T1 mapping (combined proton signal from myocytes and interstitium prior to contrast administration by the measurement of myocardial and blood relaxation time) as a means to assess myocardial fibrosis. This retrospective case-cohort over a 3-year period included all consecutive patients (aged ≤ 21 years) with advanced heart failure from dilated cardiomyopathy (echocardiographic left ventricular ejection fraction ≤ 45% and NYHA class ≥ 2) who underwent cardiac MRI.Conditional survival (follow-up ≥ 6 months after cardiac MRI) was assessed to include NYHA functional class and time to event (death or heart transplantation). A total of 57 patients (mean age 11.7 ± 6.1 years; 58% male) had a median NYHA Class III (31/57) and median left ventricular ejection fraction 25% (20-38%). Survival data were available in 82% patients (46/57) and the crude mortality rate was 24% (11/46) and one patient (2%) underwent heart transplantation. The median native T1 was elevated at 1351 ms (95% CI 1332, 1394) and it showed no difference between the groups who survived to those who died. Performing a multilevel regression analysis on prognosis failed to predict 6-month conditional survival.

Plasma microrna expression profile for reduced ejection fraction in dilated cardiomyopathy

The left ventricular (LV) ejection fraction (EF) is key to prognosis in dilated cardiomyopathy (DCM). Circulating microRNAs have emerged as reliable biomarkers for heart diseases, included DCM. Clinicians need improved tools for greater clarification of DCM EF categorization, to identify high-risk patients. Thus, we investigated whether microRNA profiles can categorize DCM patients based on their EF. 179-differentially expressed circulating microRNAs were screened in two groups: (1) non-idiopathic DCM; (2) idiopathic DCM. Then, 26 microRNAs were identified and validated in the plasma of ischemic-DCM (n = 60), idiopathic-DCM (n = 55) and healthy individuals (n = 44). We identified fourteen microRNAs associated with echocardiographic variables that differentiated idiopathic DCM according to the EF degree. A predictive model of a three-microRNA (miR-130b-3p, miR-150-5p and miR-210-3p) combined with clinical variables (left bundle branch block, left ventricle end-systolic dimension, lower systolic blood pressure and smoking habit) was obtained for idiopathic DCM with a severely reduced-EF. The receiver operating characteristic curve analysis supported the discriminative potential of the diagnosis. Bioinformatics analysis revealed that miR-150-5p and miR-210-3p target genes might interact with each other with a high connectivity degree. In conclusion, our results revealed a three-microRNA signature combined with clinical variables that highly discriminate idiopathic DCM categorization. This is a potential novel prognostic biomarker with high clinical value.

Cardiac mitofusin-1 is reduced in non-responding patients with idiopathic dilated cardiomyopathy

Prognosis of severe heart failure remains poor. Urgent new therapies are required. Some heart failure patients do not respond to established multidisciplinary treatment and are classified as “non-responders”. The outcome is especially poor for non-responders, and underlying mechanisms are largely unknown. Mitofusin-1 (Mfn1), a mitochondrial fusion protein, is significantly reduced in non-responding patients. This study aimed to elucidate the role of Mfn1 in the failing heart. Twenty-two idiopathic dilated cardiomyopathy (IDCM) patients who underwent endomyocardial biopsy of intraventricular septum were included. Of the 22 patients, 8 were non-responders (left ventricular (LV) ejection fraction (LVEF) of < 10% improvement at late phase follow-up). Electron microscopy (EM), quantitative PCR, and immunofluorescence studies were performed to explore the biological processes and molecules involved in failure to respond. Studies in cardiac specific Mfn1 knockout mice (c-Mfn1 KO), and in vitro studies with neonatal rat ventricular myocytes (NRVMs) were also conducted. A significant reduction in mitochondrial size in cardiomyocytes, and Mfn1, was observed in non-responders. A LV pressure overload with thoracic aortic constriction (TAC) c-Mfn1 KO mouse model was generated. Systolic function was reduced in c-Mfn1 KO mice, while mitochondria alteration in TAC c-Mfn1 KO mice increased. In vitro studies in NRVMs indicated negative regulation of Mfn1 by the β-AR/cAMP/PKA/miR-140-5p pathway resulting in significant reduction in mitochondrial respiration of NRVMs. The level of miR140-5p was increased in cardiac tissues of non-responders. Mfn1 is a biomarker of heart failure in non-responders. Therapies targeting mitochondrial dynamics and homeostasis are next generation therapy for non-responding heart failure patients.

Measurement of multiple cytokines for discrimination and risk stratification in patients with Chagas' disease and idiopathic dilated cardiomyopathy.

Chagas’ disease (CD), caused by the hemoflagellate protozoan, Trypanosoma cruzi, is endemic in most countries of Latin America. Heart failure (HF) is often a late manifestation of chronic CD, and is associated with high morbidity and mortality. Inflammatory processes mediated by cytokines play a key role in the pathogenesis and progression of CD. Keeping in view the inflammatory nature of CD, this study investigated the possible role of 21 different inflammatory cytokines as biomarkers for prediction and prognosis of CD. The plasma concentration of these cytokines was measured in a group of patients with CD (n = 94), and then compared with those measured in patients with dilated cardiomyopathy (DCM) from idiopathic causes (n = 48), and with control subjects (n = 25). Monovariately, plasma levels of cytokines such as stem cell growth factor beta (SCGF beta), hepatocyte growth factor (HGF), monokine induced by interferon gamma (CXCL9), and macrophage inhibitory factor (MIF) were significantly increased in CD patients with advanced HF compared to control group. None of the cytokines could demonstrate any prognostic potency in CD patients, and only MIF and stromal derived factor-1 alpha (CXCL12) showed significance in predicting mortality and necessity for heart transplant in DCM patients. However, multivariate analysis prognosticated a large proportion of CD and DCM patients. In CD patients, HGF and Interleukin-12p40 (IL-12p40) together separated 81.9% of 3-year survivors from the deceased, while in DCM patients, CXCL12, stem cell factor (SCF), and CXCL9 together discriminated 77.1% of survivors from the deceased. The significant increase in plasma concentrations of cytokines such as HGF and CXCL9 in CD patients, and the ability of these cytokines to prognosticate a large proportion of CD and DCM patients multivariately, encourages further studies to clarify the diagnostic and prognostic potential of cytokines in such patients.

Prevalence, Prognosis and Predictors of Neurological Complications after Heart Transplantation

Purpose Heart transplantation (HT) is the gold-standard treatment for end-stage heart failure. In spite of its innumerous benefits, it still involves complications. Among them, neurological complications significantly impact patient's morbidity and mortality. The aim of this study is to determine the prevalence, prognosis and predictors of neurological events after HT. Methods Between January 2007-December 2017, data from all patients who underwent orthotopic HT in this single center were collected and analyzed considering seizures, ischemic and hemorrhagic stroke as neurological complications. Univariate and multivariate analysis were performed to determine significant predictors; ROC curves were generated to establish blood pressure cutoffs that influence the presence of neurological events. Mortality between groups was evaluated through Kaplan Meier curves and Log Rank test. Results We assessed 132 patients from 15-76 years of age (mean 51.8), 73.5% men, mainly in INTERMACS profile 3 (78.8%). Etiologies included Chagas disease (26.7%), ischemic cardiomyopathy (26.7%), idiopathic dilated cardiomyopathy (24.4%) and other (22.2%). Neurological events before transplant occurred in 16.7%. The prevalence of neurological complications after HT was 17.4% (8.7% ischemic stroke, 60.9% hemorrhagic stroke, 30.4% seizures), and occurred mainly in the first 10 postoperative days (71.4%). In the multivariate analysis, the difference between systolic blood pressure (SBP) before HT and on the 3rd postoperative day was an independent predictor of neurological events (p-value 0.018; 95% CI of 1.007-1.080 OR 1.043). A cut off value of SBP gradient>31,9mmHg (64.3% sensitivity,63% specificity;AUROC 0.652) significantly increased the risk of neurological complications (p=0.006, 95%CI 1.576-14.692 OR 4.811). Presence of neurological events was related to a longer hospital stay (38.6 days for patients with events, 29.1 days for patients without, p=0.019). However, up to the first-year post-transplant, neurological complications did not impact mortality risk (p=0.191). Conclusion In this single center study, prevalence of neurological complications was high, however without impact on mortality. Systolic blood pressure elevation in the 3rd postoperative day in comparison to the pre transplant period was a significant predictor of neurological complications.

Early Antibody-Mediated Rejection in Non-Pre-Sensitized Heart Transplant Recipient

Introduction Antibody-mediated rejection (AMR) is an important cause of allograft dysfunction. It usually occurs after the first month of heart transplant (HT), but an early presentation is possible. We present an unusual case of a female HT recipient who had early AMR with no evidence of pre-sensitization to the donor. Case Report A woman, 45 years old, idiopathic dilated cardiomyopathy, two kids, with previous negative panel reactive antibody (PRA) was submitted to HT with success. The prospective crossmatch was negative and she did not receive blood cells during the surgery. The donor was a woman, 47 years old, who had a hemorrhagic stroke. After the procedure, she needed low doses of vasoactive drugs, received immunosuppression therapy according to institutional protocol and maintained normal ventricular function. On the 5th day, she developed biventricular graft dysfunction (left ventricular ejection fraction of 40%) requiring inotropes. The PRA revealed a donor specific antibody (DSA) not previously detected and the result of endomyocardial biopsy (EMB) confirmed acute AMR (pAMR2). Patient was successfully treated with methylprednisolone, plasmapheresis, immunoglobulin and rituximab. Biventricular function recovered; no DSA was detected and new EMB showed no rejection findings. Summary AMR results from recipient antibodies against donor-HLA antigens, causing complement activation, inflammation and injury to the allograft endothelium. In general, it occurs in the first two months after HT due to a rise in DSA by the contact with donor-HLA antigens. Early AMR, that occurs in the first week, is related to pre-sensitization to donor HLA antigens and associated with graft dysfunction. In this case report, no previous antibody had been detected. Two possibilities could explain such findings: the presence of non-HLA antibodies or the presence of memory B cells with levels of DSA too low to be detected on PRA. This case highlights the importance of monitoring antibodies in HT recipients with early allograft dysfunction even with previous negative PRA.

Use of SherpaPak™ CTS for Organ Transportation during Heart Transplantation: First Clinical Use in United Kingdom and Outcomes

Purpose SherpaPak™ CTS is CE marked and FDA approved device for organ transportation during heart transplantation. This device maintains organ temperature between 4-8°C which is the recommended temperature range by ISHLT 2020 consensus statement to prevent potential freezing damage. The aim of study was to analyse the outcomes and learning points from its first clinical use in United Kingdom, in our unit. Methods We prospectively collected the data on 7 consecutive patients where SherpaPak™ was used for transportation of heart from December 2019 to September 2020. We analysed the donor and recipient demographics, transport parameters and clinical outcomes of these patients. Results Patients median age was 50 years (range 19 - 61 years). Primary diagnosis was idiopathic dilated cardiomyopathy (n=4), ischaemic cardiomyopathy (n=2) and familial dilated cardiomyopathy (n=1). Median Total ischemic time was 150 minutes (IQR 120 - 213 minutes). Median transport time on SherpaPak™ was 71 minutes (IQR 53 - 129 minutes), with a median organ temperature of 5.54°C (IQR 4.66°C - 6.28°C) while median outside environment temperature was 18.58°C (IQR 17.89°C - 21.10°C). Intra-operatively, all hearts transported on SherpaPak™ were found to be soft and supple, with no frost damage. Among the 7 heart transplant patients, 4 patients were VAD explants. 1 patient required VA ECMO on day 1 for RV failure due to high pulmonary vascular resistance, while 6 did not need any mechanical support postoperatively. 5 patients have been successfully discharged from the hospital while the last 2 who had transplant done during last 2 weeks, are still inpatient and recovering in the ITU. Median ICU stay was 16 days (IQR 5-16 days) and median hospital stay was 27 days (IQR 25-34 days). Conclusion Our results demonstrate that SherpaPak™ is a safe device for organ transportation during heart transplantation. Further experience is needed to understand potential benefits and costs effectiveness

Hypertrophic Cardiomyopathy with Left Ventricular Systolic Dysfunction: Clinical Outcome after Implantable Continuous-Flow Left Ventricular Assist Device Implantation

Purpose Various patterns of disease progression have been reported in patients with hypertrophic cardiomyopathy (HCM). HCM with left ventricular systolic dysfunction (HCM-LVSD) has been recognized as unfavorable patterns of disease progression that a certain proportion of patients with HCM-LVSD finally requires heart transplantation (HTx) or implantable continuous-flow left ventricular assist device (iLVAD) implantation. Compared with dilated cardiomyopathy (DCM), HCM-LVSD has reported to demonstrate worse prognosis. However, long-term prognosis of patients with HCM-LVSD after iLVAD implantation has not been fully elucidated. This study aimed to clarify the long-term clinical outcome of patients with HCM-LVSD after iLVAD implantation in comparison with those with DCM. Methods The medical records of both patient with HCM-LVSD and idiopathic DCM as control group who underwent iLVAD implantation from 2011 to 2020 in our institution were reviewed. Results 96 patients with DCM (mean age 43.5 years, 73 males,) and 24 patients with HCM-LVSD (mean age 48.3 years, 16 males) had received iLVAD implantation (DCM: 25 centrifugal-flow and 71 axial-flow LVAD, HCM-LVSD: 10 centrifugal-flow and 14 axial-flow LVAD) with average LVAD support period of 1080 and 928 days, respectively. Although, there was no significant difference in brain natriuretic peptide (BNP) at pre LVAD implantation between both groups, BNP at 3 months post LVAD implantation in DCM group was significantly higher than that in HCM-LVSD group [88 vs 256 pg/ml, p Conclusion Despite inferior survival without LVAD, HCM-LVSD demonstrated equivalent overall survival compared with that of DCM after LVAD implantation. However, BNP at 3 months after LVAD implantation in HCM-LVSD group demonstrated higher value than that of DCM group which imply existence of persistent and progressive myocardial damage or subclinical right ventricular failure in HCM-LVSD even after LVAD implantation.

Epidemiology of Infections in Adult Heart and Lung Transplant Recipients: A Single Center Experience

<h3>Purpose</h3> Infectious complications are a common cause of morbidity and mortality among solid organ transplant (SOT) recipients. Understanding their epidemiology and outcomes is vital when planning preventative strategies. <h3>Methods</h3> We conducted a retrospective study of selected infections diagnosed in patients receiving heart (HT) or lung transplantation (LT) from January 2013 to June 2018. We examined the incidence of infections and outcomes one-year post-transplant. <h3>Results</h3> We reviewed 217 patients that underwent heart or lung transplantation (109 HT, 108 LT) at our center over a five-year period. Median follow-up was 2.5 years, median age was 51, 68% were males, and 75%-white. Indication for transplant in HT recipients was predominantly idiopathic dilated cardiomyopathy (22%) and ischemic dilated cardiomyopathy (11%). Indications for lung transplants included idiopathic pulmonary fibrosis (19%), chronic obstructive pulmonary disease (9%), and cystic fibrosis (7%). Within the first year post-transplant, 46% of transplant recipients had defined infections (56% LT, 35% HT)(Table). In the HT group, CMV (14%) respiratory viruses (9%), aspergillosis (6%), and <i>Clostridioides difficile</i> infection (6%) were most common. In the LT group, respiratory viruses (39%), aspergillosis (21%), <i>Clostridioides difficile</i> (14%), and extended-spectrum beta-lactamase producing bacteria (9%) were most common. All-cause mortality at one year was 5% and 10% in the HT and LT recipients, respectively. There was no infection-related mortality at one year in both groups. <h3>Conclusion</h3> Despite standard infection prevention strategies, nearly half of all HT and LT recipients had identified infections at the end of one year. The most frequent infectious process was respiratory viral infections, particularly in the LT group. Further studies identifying associated risk factors and additional preventative measures may be needed to reduce these infections.

Correction of Anomalous Pulmonary Venous Return during Heart Transplantation

Introduction The management of incidental cardiac shunts at the time of orthotopic heart transplantation (OHT) is rarely described in literature. We present a case involving surgical correction of a partial anomalous pulmonary venous connection (PAPVC) at the time of OHT. Case Report The patient is a 65-year-old woman with a history of idiopathic dilated cardiomyopathy (diagnosed in 2010), and a PAPVC. She was diagnosed with the PAPVC incidentally after a right heart catheterization. CT angiogram confirmed an anomalous connection of her right superior and middle pulmonary veins to her superior vena cava (SVC). Serial echocardiograms showed a left ventricular ejection fraction of 20 to 25% and mild pulmonary hypertension. Her right atrium and ventricle were mildly dilated in size and her right ventricular function remained normal. In the year preceding her OHT she developed NYHA class III-IV symptoms and frequent episodes of decompensated heart failure, necessitating advanced cardiac therapies. Ultimately she underwent OHT with concomitant PAPVC repair. At the time of transplantation, the recipient's SVC was divided above the anomalous vein and a pericardial patch was applied to the orifice created on the right atrium. The recipient right atrium and interatrial septum were constructed into an atrial baffle with bovine pericardium, which was then anastomosed to the donor left atrium with a surgically created atrial septal defect in the fossa ovalis. Afterwards, the transplantation proceeded using the standard bicaval technique with the donor left atrium connected to recipient left atrium and the atrial baffle. There were no intra-operative complications, and the patient did well post-operatively. Summary PAPVCs typically cause shunting of oxygenated blood to the right atrium. For patients with clinically significant PAPVCs, surgical correction may be necessary and usually involves a Warden procedure, which can require reconstruction of the right atrial appendage. In patients undergoing PAPVC repair at the time of bicaval OHT, the recipient SVC is anastomosed to donor SVC which is simpler technically than atrial reconstruction and offers better outcomes regarding arrhythmias and tricuspid regurgitation. Furthermore, this maintains adequate pulmonary and systemic venous outflow into the atria. To our knowledge, this is the first reported case of PAPVC repair at the time of OHT in the US.

Bidirectional Dynamic Change in Shunt Flow Across a Small Ventricular Septal Defect in a Patient With a Left Ventricular Assist Device

A 50-year-old man implanted with a durable left ventricular assist device (LVAD; HeartMate 3, Abbott Laboratories, Chicago, IL) for idiopathic dilated cardiomyopathy was transferred to our hospital for further follow-up. He had not been diagnosed with any intracardiac shunts before LVAD implantation. On admission, echocardiography revealed a small left-to-right (L-R) shunt flow across the interventricular septum, indicating muscular ventricular septal defect (VSD). As the pump speed was raised during an echocardiographic ramp test for LVAD optimization, the L-R shunt flow at low pump speed (Fig.

The corrected left ventricular ejection fraction: a potential new measure of ventricular function.

Left ventricular ejection fraction (LVEF) has a limited role in predicting outlook in heart diseases including heart failure. We quantified the independent geometric factors that determine LVEF using cardiac MRI and sought to provide an improved measure of ventricular function by adjusting for such independent variables. A mathematical model was used to analyse the independent effects of structural variables and myocardial shortening on LVEF. These results informed analysis of cardiac MRI data from 183 patients (53 idiopathic dilated cardiomyopathy (DCM), 36 amyloidosis, 55 hypertensives and 39 healthy controls). Left ventricular volumes, LVEF, wall thickness, internal dimensions and longitudinal and midwall fractional shortening were measured. The modelling demonstrated LVEF increased in a curvilinear manner with increasing mFS and longitudinal shortening and wall thickness but decreased with increasing internal diameter. Controls in the clinical cohort had a mean LVEF 64 ± 7%, hypertensives 66 ± 8%, amyloid 49± 16% and DCM 30 ± 11%. The mean end-diastolic wall thickness in controls was 8 ± 1mm, DCM 8 ± 1mm, hypertensives 11 ± 3mm and amyloid 14 ± 3mm, P < 0.0001). LVEF correlated with absolute wall thickening relative to ventricular size (R2 = 0.766). A regression equation was derived from raw MRI data (R2 = 0.856) and used to 'correct' LVEF (EFc) by adjusting the wall thickness and ventricular size to the mean of the control group. Improved quantification of the effects of geometric changes and strain significantly enhances understanding the myocardial mechanics. The EFc resulted in reclassification of a 'ventricular function' in some individuals and may provide an improved measure of myocardial performance especially in thick-walled, low-volume ventricles.

Exercise Training Improved Pulmonary Gas Exchange Abnormalities in Pulmonary Hypertension due to Heart Failure: A Case Report

Heart failure (HF) is the most common cause of pulmonary hypertension (PH), and reduced exercise capacity and exertional dyspnea are the most frequent concerns in patients with PH-HF. Indeed, carbon dioxide end-tidal partial pressure (PETCO 2 ) during exercise is a well-established noninvasive marker of ventilation/perfusion ratio in PH. We aimed to evaluate the effect of aerobic exercise training on PETCO 2 response during exercise in a 59-year-old woman with PH secondary to idiopathic dilated cardiomyopathy. The patient with [...]

Diastolic dyssynchrony in patients with LV only fusion pacing CRT without RV lead

Abstract Funding Acknowledgements Type of funding sources: None. Background CRT improves both systolic and diastolic function, thus increasing cardiac output. However, less data is available concerning diastolic dyssynchrony and fusion pacing CRT. The aim of our study was to assess the outcome of LV diastolic asynchrony in a population of fusion pacing CRT without right ventricular (RV) lead. Methods Prospective data were collected from a cohort of patients (pts) with right atrium/left ventricle leads (RA/LV CRT). Baseline and every 6 months follow-up included standard ETT and classical dyssynchrony parameter measurements. Diastolic dyssynchrony was done by offline speckle-tracking derived TDI timing assesment of the simultaneity of E" and A" basal septal and lateral wall 4 chamber view. New parameters were introduced: E" and respectively A" time (E"T / A"T) as the time difference between E" (respectively A" ) peaks septal and lateral wall. Exercise tests, drugs optimization and device individual programmimg were systematically performed in order to maintain constant fusion and improve CRT response. Patients were divided in three groups: super-responders (SR), responders (R) and non responders (NR). Results Sixty-two pts (35 male) aged 62 ± 11 y.o. with idiopathic DCM implanted with a RA/LV CRT were analyzed: 34%SR / 61%R / 5%NR. Baseline initial characteristics: QRS 164 ± 18 ms; EF 27 ± 5.2; 29% had type III diastolic dysfunction (DD), 63% type II DD, 8% type I DD. Average follow-up was 45 ± 19 months; mean LVEF at the last follow-up was 37 ± 7.9%. The E"T decreased from 90 ± 20 ms to 25 ± 10 ms in SR with significant LV reverse remodelling (LV end-diastolic volume 193.7 ± 81 vs 243.2 ± 82 ml at baseline, p &amp;lt; 0.0028) and lower LV filling pressures (E/E" 13.2 ± 4.6 vs 11.4 ± 4.5, p =0.0295). DD profile improved in 65% of R with a reduction in E/A ratio (1.46 ± 5.3 vs. 0.82 ± 3.9 at baseline, p= 0.4453). Non-sudden cardiac death occurred in 3 NR pts (2%) with type III DD, severe LA volume and larger E" T /A"T (E"T&amp;gt; 85 msec A"T &amp;gt; 30 msec). Significant cut off value calculated by ROC curve for LV diastolic dyssynchrony is E"T &amp;gt; 80 ms and A"T of &amp;gt; 25 msec. Conclusions Fusion pacing CRT without RV lead showed a positive outcome; improving LV diastolic dyssynchrony in responders and super-responders patients is obvious. Larger randomized studies are needed to define the role of diastolic asynchronism as a predictor of favorable response in fusion pacing. Abstract Figure. Typical TDI patterns in LV fusion pacing

February 2021 at a glance: focus on amyloidosis, myocarditis and cardiomyopathy

Cardiac amyloidosis (CA) is emerging as a major cause of heart failure (HF).1-3 Castiglione et al.4 reviewed the role of circulating biomarkers as tools to guide diagnosis, prognostic stratification, and therapy in CA. The independent prognostic role of cardiopulmonary exercise testing in patients with light chain or transthyretin CA (TTR-CA) was shown by Nicol et al.5 in a multicentre study. Both peak oxygen consumption (VO2) ≤13 mL/kg/min and N-terminal pro B-type natriuretic peptide (NT-proBNP) ≥1800 ng/L had independent prognostic value with a hazard ratio (HR) of 2.7 [95% confidence interval (CI) 1.6–4.8] and 2.2 (95% CI 1.1–4.3), respectively. No events occurred in patients with peak VO2 >13 mL/kg/min and NT-proBNP <1800 ng/L during a median follow-up of 20 months, despite overall 25% mortality and 29% hospitalization rates. Amyloidosis may be present in patients with severe aortic stenosis.2, 6 TTR-CA was detected in 13% of patients with severe aortic stenosis undergoing transcatheter aortic valve replacement. It had no impact on mortality but was associated with a higher HF hospitalization rate during a 3-year follow-up.3 Tafamidis has emerged as an effective treatment option to improve prognosis in patients with TTR-CA.7, 8 A single-centre study in 648 real-world patients with TTR-CA matching the inclusion criteria of the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT) showed a significant benefit of tafamidis on major cardiovascular outcomes (HR after propensity score matching 0.546, P = 0.0132).9 In an analysis of the long-term extension of ATTR-ACT, both tafamidis 80 mg and 20 mg reduced all-cause mortality and cardiovascular hospitalizations at 30 months compared with placebo, with the higher dose associated with better outcomes without safety issues in the long-term extension.10 Sinagra et al.11 reviewed data about the role of viral detection for immunomodulation in acute lymphocytic myocarditis, highlighting current limitations of this approach and providing a framework for future dedicated studies. The Authors pointed out that the value of viral presence to guide immunosuppressive treatment in lymphocytic myocarditis requires more evidence and remains a subject of debate. As a further support, intravenous immunoglobulin did not improve cardiac systolic function or functional status in patients with chronic inflammatory cardiomyopathy, namely idiopathic dilated cardiomyopathy with parvovirus B19 persistence, in a randomized controlled trial.12 Over the last years, improvement in survival was observed in patients with dilated cardiomyopathy, with many patients with new-onset cardiomyopathy who may show reverse remodelling.13, 14 In TRED-HF, withdrawal of pharmacological treatment for HF in patients with recovered dilated cardiomyopathy was associated with relapses in 44% of patients.15 In a further analysis by cardiac magnetic resonance, treatment withdrawal resulted in early ventricular remodelling with an increase in myocardial mass and a reduction in global longitudinal strain. Interestingly, these changes may also occur in patients who do not show clinical deterioration.16 Shorter left ventricular systolic ejection time has been identified as a marker of worse prognosis among patients with HF with reduced ejection fraction (HFrEF).17 Alhakak et al.18 confirmed the prognostic impact of left ventricular systolic ejection time on mortality in a large HFrEF population (per 10 ms decrease: adjusted HR 1.06, 95% CI 1.01–1.11, P = 0.030), hence supporting its use to stratify patients' risk and to guide therapeutic response. Heightened chemosensitivity has a major role in the excessive ventilatory response to exercise and sleep breathing abnormalities in patients with HF. Buspirone, a 5HT1A receptor agonist that inhibits serotonergic chemoreceptor neuron firing, reduced carbon dioxide chemosensitivity and improved central apnoeas in patients with HF.19 A relatively large number of patients with advanced HF may benefit from long-term mechanical circulatory support.20 This indication might be further expanded if this device therapy may cause regression of myocardial fibrosis. Unfortunately, such hypothesis was not proven in a recent study in 125 patients.21

Intravenous immunoglobulin therapy in adult patients with idiopathic chronic cardiomyopathy and cardiac parvovirus B19 persistence: a prospective, double-blind, randomized, placebo-controlled clinical trial.

AimsPrevious uncontrolled studies suggested a possible benefit of intravenous immunoglobulin (IVIg) in parvovirus B19 (B19V)‐related dilated cardiomyopathy (DCM). This randomized, double‐blind, placebo‐controlled, single‐centre trial investigated the benefits of IVIg beyond conventional therapy in idiopathic chronic DCM patients with B19V persistence.Methods and resultsFifty patients (39 men; mean age 54 ± 11 years) with idiopathic chronic (>6 months) DCM on optimal medical therapy, left ventricular ejection fraction (LVEF) <45%, and endomyocardial biopsy (EMB) B19V load of >200 copies/µg DNA were blindly randomized to either IVIg (n = 26, 2 g/kg over 4 days) or placebo (n = 24). The primary outcome was change in LVEF at 6 months after randomization. Secondary outcomes were change in functional capacity assessed by 6‐min walk test (6MWT), quality of life [Minnesota Living with Heart Failure Questionnaire (MLHFQ)], left ventricular end‐diastolic volume (LVEDV), and EMB B19V load at 6 months after randomization. LVEF significantly improved in both IVIg and placebo groups (absolute mean increase 5 ± 9%, P = 0.011 and 6 ± 10%, P = 0.008, respectively), without a significant difference between groups (P = 0.609). Additionally, change in 6MWT [median (interquartile range) IVIg 36 (13;82) vs. placebo 32 (5;80) m; P = 0.573], MLHFQ [IVIg 0 (−7;5) vs. placebo −2 (−6;6), P = 0.904] and LVEDV (IVIg −16 ± 49 mL/m2 vs. placebo −29 ± 40 mL/m2; P = 0.334) did not significantly differ between groups. Moreover, despite increased circulating B19V antibodies upon IVIg administration, reduction in cardiac B19V did not significantly differ between groups.ConclusionIntravenous immunoglobulin therapy does not significantly improve cardiac systolic function or functional capacity beyond standard medical therapy in patients with idiopathic chronic DCM and cardiac B19V persistence.Clinical Trial Registration: ClinicalTrials.gov ID NCT00892112.