Biosensors with left ventricular assist devices.

Heart failure imposes a significant global health burden, standing as a primary contributor to mortality. Various indicators and physiological shifts within the body may hint at distinct cardiac conditions. Specific biosensors have the capability to identify these changes. Integrating or embedding these biosensors into mechanical circulatory support devices (MCSDs), such as left ventricular assist devices (LVADs), becomes crucial for monitoring alterations in biochemical and physiological factors subsequent to an MCSD implantation. Detecting abnormal changes early in the course of disease progression will allow for improved patient outcomes and prognosis following an MCSD implantation. The aim of this review is to explore the available biosensors that may be coupled or implanted alongside LVADs to monitor biomarkers and changes in physiological parameters. Different fabrication materials for the biosensors are discussed, including their advantages and disadvantages. This review also examines the feasibility of integrating feedback control mechanisms into LVAD systems using data from the biosensors. Challenges facing this emerging technology and future directions for research and development are outlined as well. The overarching goal is to provide an overview of how implanted biosensors may improve the performance and outcomes of LVADs through continuous monitoring and closed-loop control.

Large animal models to study effectiveness of therapy devices in the treatment of heart failure with preserved ejection fraction (HFpEF).

Our understanding of the complex pathophysiology of Heart failure with preserved ejection fraction (HFpEF) is limited by the lack of a robust in vivo model. Existing in-vivo models attempt to reproduce the four main phenotypes of HFpEF; ageing, obesity, diabetes mellitus and hypertension. To date, there is no in vivo model that represents all the haemodynamic characteristics of HFpEF, and only a few have proven to be reliable for the preclinical evaluation of potentially new therapeutic targets. HFpEF accounts for 50% of all the heart failure cases and its incidence is on the rise, posing a huge economic burden on the health system. Patients with HFpEF have limited therapeutic options available. The inadequate effectiveness of current pharmaceutical therapeutics for HFpEF has prompted the development of device-based treatments that target the hemodynamic changes to reduce the symptoms of HFpEF. However, despite the potential of device-based solutions to treat HFpEF, most of these therapies are still in the developmental stage and a relevant HFpEF in vivo model will surely expedite their development process. This review article outlines the major limitations of the current large in-vivo models in use while discussing how these designs have helped in the development of therapy devices for the treatment of HFpEF.

Is the child at risk? Cardiovascular remodelling in children born to diabetic mothers.

OBJECTIVE: The objective of this study was to assess differences in myocardial systolic and diastolic function and vascular function in children 2-5 years of age born to diabetic as compared to non-diabetic mothers. METHODS: This study was a retrospective cohort conducted in 2016 at The Aga Khan University Hospital, Karachi, Pakistan. It included children between 2 and 5 years of age born to mothers with and without exposure to diabetes in utero (n = 68 in each group) and who were appropriate for gestational age. Myocardial morphology and function using echocardiogram and carotid intima media thickness (cIMT) and pulse wave velocity was performed to evaluate cardiac function as well as macrovascular remodelling in these children. Multiple linear regression was used to compare the groups. RESULTS: There was no significant difference in cardiac morphology, myocardial systolic and diastolic function, and macrovascular assessment between the exposed and unexposed groups of AGA children. Subgroup analysis demonstrated a significantly decreased mitral E/A ratio in children whose mothers were on medications as compared to those on dietary control (median [IQR] = 1.7 [1.6-1.9] and 1.56 [1.4-1.7], respectively, p = 0.02), and a higher cIMT in children whose mothers were on medication as compared to controls (0.48 [0.44-0.52] and 0.46 [0.44-0.50], respectively, p = 0.03). CONCLUSION: In utero exposure to uncontrolled maternal diabetes has an effect on the cardiovascular structure and function in children aged 2-5 years. However, future work requires long-term follow-up from fetal to adult life to assess these changes over the life course.

Quality improvement initiative in paediatric echocardiography laboratory in a low- to middle-income country.

AIMS: To determine the impact of a quality improvement (QI) initiative in the area of paediatric echocardiography (echo) in a low- to middle-income country (LMIC).Care for patients with congenital heart disease is challenging, especially in LMICs. Collaborative learning through QI projects is imperative to ensure improvement in delivery processes leading to better patient outcomes. METHODS AND RESULTS: This QI initiative was taken by a team consisting of physicians and sonographers. Problems were identified, a key driver diagram (KDD) was created, and simple process re-engineering was done using interventions based on the KDD. Metrics (five process and one outcome) were assessed to determine the effectiveness of the QI project. The process metrics assessed were comprehensiveness of exam, timeliness of reporting, diagnostic accuracy and error, and sedation adverse event rates of transthoracic echocardiograms, while a novel comprehensive echo laboratory (lab) quality score was developed as an outcome metric. Data were collected quarterly and analysed in the post-implementation phase. Significant improvement was seen in comprehensive mean score (20.4-29.7), timeliness (40-95%), and diagnostic accuracy rate (91-100%), while a decrease was seen in the diagnostic error rate (7.5-3.5%) and the sedation adverse event rate (6.8-0%), pre- vs. post-implementation. The overall quality outcome score improved from 7 to 19 and the echo lab was able to achieve adequate quality. CONCLUSION: This QI initiative produced improvement in all the processes, and the overall quality of the echo lab without any substantial increase in resources or cost.

Murmur and Doppler alternans in critical pulmonary stenosis.

Pulsus alternans is a well-recognized clinical entity in which alternating strong and weak pulses are detected. It usually is secondary to underlying myocardial failure. Murmur alternans (alternation in murmur intensity) has been described in aortic stenosis and a few right-sided lesions such as pulmonary hypertension and embolism. This report describes a case of murmur alternans in critical pulmonary stenosis that also showed Doppler alternans on echocardiography. The underlying cause was right ventricular systolic dysfunction.

Cardiovascular Dysfunction in Children Exposed to Preeclampsia During Fetal Life.

BACKGROUND: Keeping in view the developmental origin of health and disease hypothesis, the aim of this study was to assess differences in cardiac and vascular structure and function in children exposed to preeclampsia in utero compared with those of normotensive mothers. The hypothesis under investigation was that children exposed to preeclampsia would have altered cardiac and vascular structure and function compared with the unexposed group. METHODS: This was a retrospective cohort study that included children 2 to 10 years of age born to mothers with and without exposure to preeclampsia in utero (n = 80 in each group). Myocardial morphology and function using echocardiography and carotid intima-media thickness and pulse-wave velocity were determined. Multivariate linear regression was used to compare preeclampsia-exposed and nonexposed groups. Subgroup analysis to assess differences between early- and late-onset preeclampsia was also performed. RESULTS: Forty-one percent of mothers (n = 33) had early-onset preeclampsia. Children in the exposed group had a significantly higher prevalence of stage 1 systolic and diastolic hypertension (22% [n = 18] and 35% [n = 18], respectively) compared with the unexposed group (9% [n = 7] and 19% [n = 15], respectively; P = .01). Children in the exposed group also had higher pulse-wave velocity compared with those in the unexposed group (0.42 ± 0.1 vs 0.39 ± 0.1, P = .03). Subgroup analysis revealed that changes in blood pressure and pulse-wave velocity were determined primarily by early-onset preeclampsia. There was no significant difference in cardiac morphology or systolic and diastolic function between the exposed and unexposed groups. CONCLUSION: In utero exposure to preeclampsia has an effect on vascular function in children aged 2 to 10 years, related primarily to early-onset disease. Routine blood pressure screening should be recommended for such children.

Multisystem inflammatory syndrome (MIS-C) in Pakistani children: A description of the phenotypes and comparison with historical cohorts of children with Kawasaki disease and myocarditis.

OBJECTIVES: To determine clinical, laboratory features and outcomes of Multisystem Inflammatory Syndrome in children (MIS-C) and its comparison with historic Kawasaki Disease (KD) and Viral Myocarditis (VM) cohorts. METHODS: All children (1 month- 18 years) who fulfilled the World Health Organization criteria of MIS-C presenting to two tertiary care centers in Karachi from May 2020 till August 31st were included. KD and VM admitted to one of the study centers in the last five years prior to this pandemic, was compared to MIS-C. RESULTS: Thirty children with median age of 24 (interquartile range (IQR)1-192) months met the criteria for MIS-C. Three phenotypes were identified, 12 patients (40%) with KD, ten (33%) VM and eight (26%) had features of TSS. Echocardiography showed coronary involvement in 10 (33%), and moderate to severe Left Ventricular dysfunction in 10 (33%) patients. Steroids and intravenous immunoglobulins (IVIG) were administered to 24 (80%) and 12 (41%) patients respectively while 7 (23%) received both. Overall, 20% children expired. During the last five years, 30 and 47 children were diagnosed with KD and VM, respectively. Their comparison with MIS-C group showed lymphopenia, thrombocytosis, and higher CRP as well as more frequent atypical presentation in MIS-C KD group with less coronary involvement. The MIS-C VM was more likely to present with fulminant myocarditis. CONCLUSIONS: Our MIS-C cohort is younger with higher mortality compared to previous reports. MIS-C is distinct from historic cohorts of KD and VM in both in clinical features and outcomes.

Congenital bilateral choanal atresia.

Congenital choanal atresia (CCA) is the developmental failure of the nasal cavity to communicate with nasopharynx. Surgical repair is recommended in the first weeks of life in bilateral cases because this is a life-threatening situation in newborns. This is a case report of a full-term, healthy newborn baby presenting with intermittent attacks of cyanosis and respiratory distress soon after birth. On examination, alternating cyanosis and normal colour was observed in the infant. The insertion of nasal catheters in both the nares revealed the diagnosis of bilateral CCA. For this rare condition, conservative management was followed with elective transnasal endoscopic repair to relieve the life threatening nasal obstruction at the tenth day of life.

Cardiac Abnormalities Seen in Pediatric Patients During the SARS-CoV2 Pandemic: An International Experience.

Background During the SARS-CoV2 pandemic, there has been increase in hyperinflammatory presentation in previously healthy children with a variety of cardiac manifestations. Our objective is to describe the cardiac manifestations found in an international cohort of 55 pediatric cases with multi-system inflammatory syndrome (MIS-C) during the SARS-CoV2 pandemic. Methods and Results We reviewed data on previously healthy pediatric patients (≤18 years) with structurally normal hearts who presented at hospitals in the United States, United Kingdom, Spain and Pakistan with MIS-C and had consultation with a pediatric cardiologist. Data collected included demographics, clinical presentation, laboratory values, electrocardiographic abnormalities, echocardiographic findings and initial therapies. A total of 55 patients presented with MIS-C. Thirty-five patients (64%) had evidence of decreased left ventricular function, 17 (31%) had valvulitis, 12 (22%) with pericardial effusion and 11 (20%) with coronary abnormalities. Twenty-seven (49%) required ICU admission and 24 (44%) had evidence of shock. Eleven patients (20%) fulfilled complete Kawasaki disease criteria and had lower NT pro-BNP, D-dimer and ferritin levels compared with those who did not fulfill criteria. Electrophysiologic abnormalities occurred in 6 patients and included complete atrioventricular (AV) block, transient AV block and ventricular tachycardia. Conclusions We describe the first international cohort of pediatric patients with MIS-C during the SARS-CoV2 pandemic with a range of cardiac manifestations. This paper brings awareness and alertness to the global medical community to recognize these children during the pandemic and understand the need for early cardiology evaluation and follow-up.

Impact of Congenital Cardiac Catheterization Project on Outcomes-Quality Improvement (C3PO-QI) in LMICs.

BACKGROUND: The importance of registries for collaborative quality improvement has been overlooked in low/middle-income countries (LMIC). Aga Khan University Hospital (AKUH) in Pakistan joined the Congenital Cardiac Catheterization Project on Outcomes-Quality Improvement (C3PO-QI) in March 2017 with the goal of leveraging international collaboration to improve patient care and institutional standards. METHODS: The C3PO-QI key driver-based approach was used, with certain modifications, for process re-engineering in AKUH's congenital cardiac catheterisation laboratory (CCL) to reduce radiation exposure during cardiac catheterisation procedures (the primary outcome of C3PO- QI). Educating staff and standardising procedural documentation were the principal goals of the process re-engineering. Data survey was used to assess staff knowledge, attitude and practice before and after the initiative. Additionally, case demographics and outcomes were compared between AKUH and C3PO-QI centres. RESULTS: There was an increase in appropriate recording of radiation surrogates (0%-100%, p=0.00) and in the percentage of cases that met the established benchmark of 'Ideal documentation' (35% vs 95%, p=0.001). There was also an increase in self-reported staff interest during the case (25% vs 75%, p=0.001). AKUH versus C3PO-QI data showed similar demographic characteristics. There was a slight over-representation of diagnostic cases (42% vs 32%) as compared with interventional (58% vs 68%) at AKUH. Furthermore, interventional procedures were predominately PDA and ASD device closures (n=19 and 15, respectively). The frequency of adverse events were the same between AKUH and collaborative sites. CONCLUSION: Collaborative efforts between developed and LMIC CCL are significant in advancing system-level processes.

Solitary infantile myofibromatosis of the skull.

This is the report of a 6 months old boy presenting with a firm, solitary mass on the temporal region, associated with lysis of local bone. Investigations lead to a diagnosis of infantile myofibromatosis (IM). Wide local excision was performed. At one year follow-up, no recurrence was noted.

Impact of International Quality Improvement Collaborative on Congenital Heart Surgery in Pakistan.

BACKGROUND: The International Quality Improvement Collaborative (IQIC) was formed to reduce mortality and morbidity from congenital heart disease (CHD) surgeries in low/middle-income countries. OBJECTIVES: We conducted this study to compare the postoperative outcomes of CHD surgeries at a centre in Pakistan before and after joining IQIC. METHODS: The IQIC provides guidelines targeting key drivers responsible for morbidity and mortality in postoperativepatients with CHD. We focused primarily on nurse empowerment and improving the infection control strategies at our centre. Patients with CHD who underwent surgery at this site during the period 2011-2012 (pre-IQIC) were comparedwith those getting surgery in 2013-2014 (post-IQIC). Morbidity (major infections), mortality and factors associated with them were assessed. RESULTS: There was a significant decrease in surgical site infections and bacterial sepsis in the post-IQIC versus pre-IQIC period (1% vs 30%, p=0.0001, respectively). A statistically insignificant decrease in the mortality rate was also noted in post-IQIC versus pre-IQIC period (6% vs 9%, p=0.17, respectively). Durations of ventilation and intensive care unit (ICU) and hospital stay were significantly reduced in the post-IQIC period. Age <1 year, malnutrition, low preoperative oxygen perfusion, Risk Adjustment for Congenital Heart Surgery score >3, major chromosomal anomalies, perfusion-related event, longer ventilation and ICU/hospital stay durations were associated with greater odds of morbidity and mortality. CONCLUSION: Enrolling in the IQIC programme was associated with an improvement in the postsurgical outcomes of the CHD surgeries at our centre.

Lowest Glucose Variability and Hypoglycemia Are Observed With the Combination of a GLP-1 Receptor Agonist and Basal Insulin (VARIATION Study).

OBJECTIVE: There is a dearth of published literature comparing glucose variability (GV) between different insulin regimens in type 2 diabetes. This cohort study compares GV using continuous glucose monitoring (CGM) in patients with well-controlled type 2 diabetes using four common insulin regimens: basal insulin + oral drugs (BO), basal insulin + glucagon-like peptide 1 receptor agonist (GLP-1 RA) (BGLP), premixed insulin (PM), and basal-bolus insulin (BB). RESEARCH DESIGN AND METHODS: Consecutive patients from three endocrinology clinics who met study criteria-type 2 diabetes, age 18 to 80 years, BMI ≤ 45 kg/m2, stable insulin regimen for a minimum of 6 months, and stable A1C value ≤7.5% (58 mmol/mol) before study enrollment-underwent 6-day masked CGM. Hypoglycemia was defined as a sensor glucose concentration <70 mg/dL on CGM. RESULTS: A total of 160 patients with comparable baseline characteristics formed four equal insulin regimen cohorts. The daily glucose SD (the primary outcome) was significantly lower in the BGLP cohort versus the BO, PM, and BB cohorts (P = 0.03, P = 0.01, and P < 0.01, respectively), and remained so after adjusting for age, BMI, type 2 diabetes duration, and A1C. Similarly, daily hypoglycemia outcomes on CGM were least for the BGLP cohort. CONCLUSIONS: The lowest GV and lowest hypoglycemia were observed in patients using the combination of basal insulin with a GLP-1 RA, supporting the complementary glycemic action of these agents in type 2 diabetes. These observed benefits in GV and hypoglycemia may contribute to the cardiovascular outcome reduction seen with GLP-1 RA therapy and should be investigated further.

Atrial Thrombus in a Premature Newborn Following Cardio-Pulmonary Resuscitation.

Critically ill newborns, whether term or preterm, are at great risk for developing symptomatic thromboembolic disease. Comorbidities like inflammation, DIC, fluctuations in cardiac output, congenital heart disease, as well as central venous or arterial catheters, are the predisposing risk factors. Clinically symptomatic or asymptomatic cases are usually picked up by echocardiography, usually done for other indications. Management usually comprises of observation, heparin therapy, thrombo-embolectomy, and catheter directed revascularization. We present a case of premature neonate who developed thrombus at inter-atrial septum as a possible consequence of cardiopulmonary resuscitation, detected by echocardiography. Conversely, there is always a possibility of paradoxical emboli in neonates with patent foramen ovale (PFO). Subsequent clinical course remained asymptomatic and baby was discharged home after 6 weeks with cardiac follow-up. Atrial septal findings of organized clot/thrombus in asymptomatic newborns need to be correlated with the details of neonatal care. Long-term follow-up is dependent on underlying pathology.

Distinctive Hemodynamics in the Immediate Postoperative Period of Patients with a Longer Cardiac Intensive Care Stay Post-Tetralogy of Fallot Repair.

OBJECTIVE: After complete surgical repair the majority of tetralogy of Fallot (ToF), patients stay ≤2 days in the Cardiac Intensive Care Unit (CICU) while some may stay longer. We undertook this study to investigate the factors associated with shorter vs. longer length of stay in the CICU to help manage resources effectively. DESIGN: Patients who underwent ToF repair at Aga Khan University, Pakistan, between July 2006 and December 2011 were studied in a case-control design. Clinical parameters were compared between short stay group (SSG) (≤2 days) and long stay group (LSG) (>2 days). Odds ratios were calculated, and regression was performed. RESULTS: Ninety-eight patients (LSG 65, SSG 33) were included. Patients with lower preoperative saturation were 2.67 times more likely to be in the LSG group (P = .02). At 4 hours postoperatively, patients with a higher inotropic score (odds ratio [OR] = 3.03, confidence interval [CI] = 1.19-7.7, P = .02), higher central venous pressure (OR = 3.04, CI = 1.27-7.32, P = .013), and significant tachycardia at 4 hours (OR = 3.5, CI = 1.19-10.3. P = .02) were at risk for having a prolonged CICU stay. On multivariate analysis, significant postoperative tachycardia at 4 hours (z-score ≥3) was highly specific (sensitivity = 38.5%, specificity = 84.9%) for predicting the chances of being in the LSG. Other predictors included preop O(2) saturation ≤82.5% (sensitivity = 61.1%, specificity = 63.0%) and CVP ≥10 mm Hg at 4 hours (sensitivity = 55.4%, specificity = 71.9%). CONCLUSION: Patients who end up staying longer in the CICU have features that are distinctive in the immediate postoperative period, and this can help clinicians in identifying patients who may need more support.

Transcatheter closure of small-to-large patent ductus arteriosus with different devices: queries and challenges.

UNLABELLED: Transcatheter closure of patent ductus arteriosus (PDA) has been in place for more than three decades. We share our experience with the newer devices. PATIENTS AND METHODS: Ninety-eight patients, with a mean age of 64 +/- 11 months (range 7 months to 54 years), underwent attempted transcatheter closure of PDA. Thirty-seven patients were infants and 10 were adults. Two patients had residual PDA after surgical ligation. There were 66 females and 32 males. RESULTS: Sixty-six patients were symptomatic and 32 were asymptomatic. Cardiac catheterization showed significant pulmonary hypertension in 18. The mean size of the PDA on aortogram was 3.1 +/- 1.4 mm (range 1.1 to 11 mm). Seven patients were referred for surgical ligation. The PDAs of 37 patients were closed using coil devices, 52 with Amplatzer duct occluders (ADO) and two with Amplatzer muscular VSD devices. One patient had a very large PDA which was embolized and retrieved surgically. One patient required occlusion with two coils. The occlusion rate in the catheterization laboratory with coils was 84 +/- 7%, and 83% with ADO. After 1 week, the occlusion rate for coils was 96%, and 99% with ADO. One patient with a large PDA requiring a 14/12 ADO was left with a mild gradient of 9 mmHg in the aorta at the end of the procedure. None of our patients had stenosis of the left pulmonary artery. CONCLUSION: Transcatheter closure of PDA is the preferred alternative to surgical ligation, which should be reserved for small infants and premature babies or large unfavorably-shaped ducts.