Angiotensin Receptor-Neprilysin Inhibition in Patients With STEMI vs NSTEMI.

BACKGROUND: Patients who sustain an acute myocardial infarction (AMI), including ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI), remain at high risk for heart failure (HF), coronary events, and death. Angiotensin-converting enzyme inhibitors have been shown to significantly decrease the risk for cardiovascular events in both STEMI and NSTEMI patients. OBJECTIVES: The objectives were to determine whether angiotensin-receptor blockade and neprilysin inhibition with sacubitril/valsartan, compared with ramipril, has impact on reducing cardiovascular events according to the type of AMI. METHODS: The PARADISE-MI (Prospective ARNI versus ACE inhibitor trial to DetermIne Superiority in reducing heart failure Events after Myocardial Infarction) trial enrolled patients with AMI complicated by left ventricular dysfunction and/or pulmonary congestion and at least 1 risk-enhancing factor. Patients were randomized to either sacubitril/valsartan or ramipril. The primary endpoint was death from cardiovascular causes or incident HF. In this prespecified analysis, we stratified patients according to AMI type. RESULTS: Of 5,661 enrolled patients, 4,291 (75.8%) had STEMI. These patients were younger and had fewer comorbidities and cardiovascular risk factors than NSTEMI patients. After adjustment for potential confounders, the risk for the primary outcome was marginally higher in NSTEMI vs STEMI patients (adjusted HR: 1.19; 95% CI: 1.00-1.41), with borderline statistical significance (P = 0.05). The primary composite outcome occurred at similar rates in patients randomized to sacubitril/valsartan vs ramipril in STEMI (10% vs 12%; HR: 0.87; 95% CI: 0.73-1.04; P = 0.13) and NSTEMI patients (17% vs 17%; HR: 0.97; 95% CI: 0.75-1.25; P = 0.80; P interaction = 0.53). CONCLUSIONS: Compared with ramipril, sacubitril/valsartan did not significantly decrease the risk for cardiovascular death and HF in patients with AMI complicated by left ventricular dysfunction, irrespective of the type of AMI. (Prospective ARNI vs ACE Inhibitor Trial to Determine Superiority in Reducing Heart Failure Events After MI; NCT02924727).

Role of Iron Therapy in Heart Failure: A Consensus Statement from India.

Iron deficiency (ID) with or without anemia is frequently observed in patients with heart failure (HF). Uncorrected ID is associated with higher hospitalization and mortality in patients with acute HF (AHF) and chronic HF (CHF). Hence, in addition to chronic renal insufficiency, anemia, and diabetes, ID appears as a novel comorbidity and a treatment target of CHF. Intravenous (IV) ferric carboxymaltose (FCM) reduces the hospitalization risk due to HF worsening and improves functional capacity and quality of life (QOL) in HF patients. The current consensus document provides criteria, an expert opinion on the diagnosis of ID in HF, patient profiles for IV FCM, and correct administration and monitoring of such patients.

Angiotensin Receptor-Neprilysin Inhibitor Therapy and Cardiac Remodeling in Heart Failure: Consensus Statement from India.

Adverse cardiac remodeling refers to progressive structural and functional modifications in the heart because of increased wall stress in the myocardium, loss of viable myocardium, and neurohormonal stimulation. The guideline-directed medical therapy for Heart failure (HF) includes Angiotensin receptor-neprilysin inhibitor (ARNI) (sacubitril/valsartan), ß-blockers, sodium-glucose co-transporter 2 (SGLT2) inhibitors, and mineralocorticoid receptor antagonists (MRA). ARNI is under-prescribed in India despite its attractive safety and efficacy profile. Therefore, the consensus discusses objectives and topics related to ARNI in the management of cardiac remodeling, and experts shared their views on the early timely intervention of effective dosage of ARNI to improve the diagnosis and enhance mortality and morbidity benefits in cardiac reverse remodeling (CRR).

Position statement from the Indian Society of Gastroenterology, Cardiological Society of India, Indian Academy of Neurology and Vascular Society of India on gastrointestinal bleeding and endoscopic procedures in patients on antiplatelet and/or anticoagulant therapy.

Antiplatelet and/or anticoagulant agents (collectively known as antithrombotic agents) are used to reduce the risk of thromboembolic events in patients with conditions such as atrial fibrillation, acute coronary syndrome, recurrent stroke prevention, deep vein thrombosis, hypercoagulable states and endoprostheses. Antithrombotic-associated gastrointestinal (GI) bleeding is an increasing burden due to the growing population of advanced age with multiple comorbidities and the expanding indications for the use of antiplatelet agents and anticoagulants. GI bleeding in antithrombotic users is associated with an increase in short-term and long-term mortality. In addition, in recent decades, there has been an exponential increase in the use of diagnostic and therapeutic GI endoscopic procedures. Since endoscopic procedures hold an inherent risk of bleeding that depends on the type of endoscopy and patients' comorbidities, in patients already on antithrombotic therapies, the risk of procedure-related bleeding is further increased. Interrupting or modifying doses of these agents prior to any invasive procedures put these patients at increased risk of thromboembolic events. Although many international GI societies have published guidelines for the management of antithrombotic agents during an event of GI bleeding and during urgent and elective endoscopic procedures, no Indian guidelines exist that cater to Indian gastroenterologists and their patients. In this regard, the Indian Society of Gastroenterology (ISG), in association with the Cardiological Society of India (CSI), Indian Academy of Neurology (IAN) and Vascular Society of India (VSI), have developed a "Guidance Document" for the management of antithrombotic agents during an event of GI bleeding and during urgent and elective endoscopic procedures.

Suspecting and diagnosing transthyretin amyloid cardiomyopathy (ATTR-CM) in India: An Indian expert consensus.

Transthyretin cardiac amyloidosis (ATTR-CM) is a rare and under-recognized disorder characterized by the aggregation of transthyretin-derived insoluble amyloid fibrils in the myocardium. Heterogeneity of symptoms at presentation, makes its diagnosis often delayed. An expert panel gathered on a virtual platform across India to conduct a meeting for developing a guiding tool for ATTR-CM diagnosis. The panel recommended younger age (≥40 years) for suspecting ATTR-CM and thick-walled non-dilated hypokinetic ventricle was considered as one of the important red flags. Electrocardiogram (ECG) and echocardiography (ECHO) findings were recommended as primary tests to raise the suspicion while nuclear scintigraphy and hematological tests were recommended to confirm the diagnosis and rule out amyloid light-chain (AL) amyloidosis. Cardiac magnetic resonance (CMR) and biopsy were recommended in case of ambiguity in the presence of red flags. Considering the lack of expert guidelines in the Indian scenario, a standardized diagnostic algorithm was also proposed.

Parenteral Iron Therapy in Patients with Heart Failure in a Resource Constrained Setting In India - Our Experience.

OBJECTIVES: To assess the prevalence of Iron Deficiency and impact of Parenteral Iron therapy in patients with Symptomatic Heart failure, the role of exercise capacity and serial Echocardiography in assessing treatment response. METHODS: Study was performed in a Government Hospital for 24 months, December 2017 to December 2019.120 participants were recruited. Patients with symptomatic heart failure and Serum Ferritin <100 mg/dl were recruited and those with diagnosed Ischemic Cardiomyopathy or unwilling to give consent were excluded. They underwent a functional assessment and 2D Echo at baseline, after 30 and 90 days of IV Carboxymaltose. The data was analysed represented in appropriate figures. A P value <0.05 was considered significant. RESULTS: Of 120 patients recruited, 28 were male and 92 were female. The mean age of presentation was 44 +/- 5.4 years. The Mean baseline Haemoglobin was 11.7 +/- 0.38 gm/dl.The baseline Ferritin levels were 16.69 +/-2.9 ug/L. HFpEF was predominant with 65% cases. The NYHA status and 6min HWT tests showed a statistically significant improvement and Echocardiography findings showed a statistically insignificant improvement after Parenteral Iron. CONCLUSION: Iron Deficiency is a major risk factor in Heart Failure including HFpEF and prevails in the younger population.Parenteral Iron Carboxymaltose followed by oral iron supplementation is effective in Heart Failure patients, especially in HFpEF. Functional capacity and NYHA status appear to be the time tested markers for Iron repletion.

Anomalous origin of coronary artery from the opposite aortic sinus of Valsalva-a single center experience with a therapeutic conundrum.

BACKGROUND: Coronary artery anomalies are rare congenital abnormalities, most often found incidentally on conventional coronary angiography and CT angiography (CTA). CTA better delineates the origin and course of anomalous coronaries. Anomalous origin of coronary artery from the opposite aortic sinus of Valsalva (ACAOS) has a prevalence of 1% with a very few having an interarterial (malignant) course. There is limited literature, especially in the Indian population, dealing with this topic. METHODS: In this retrospective observational study, angiographic data of 8500 consecutive patients from June 2011 to December 2019 at a large tertiary care hospital in western India was analyzed. Patients diagnosed with ACAOS underwent CTA for delineation of the exact anatomy. Those with a non-malignant course with evidence of ischemia clinically or on stress myocardial perfusion imaging (MPI), underwent PCI. Others with a non-malignant course were medically managed. Patients with malignant (interarterial) course were revascularized by coronary artery bypass graft (CABG) surgery in case of LCA involvement or positive MPI test. Asymptomatic patients with negative MPI were managed medically. Clinical follow-up over 12 months of patients undergoing PCI and those with a malignant course showed no major adverse cardiovascular events (MACE). RESULTS: Of the 8500 patients studied, 74 (0.87%) had ACAOS. Of these, 51 (68.9%) patients had anomalous origin of right coronary artery (RCA) from the left aortic sinus, 21 (28.4%) had anomalous origin of the circumflex artery (Cx) from the right aortic sinus and two patients (2.7%) had an anomalous origin of the left main coronary artery (LCA) from the right aortic sinus. Interarterial course was found in five (6.7%) patients. Of these, four patients underwent CABG-one asymptomatic patient with LCA from right aortic sinus and three with positive MPI in anomalous RCA. All five patients with malignant course and ten patients who underwent PCI were free of MACE over 12 months' clinical follow up. CONCLUSIONS: ACAOS is a rare anomaly and if interarterial course is excluded, then PCI is feasible in selected cases with significant stenosis. Patients with malignant course with inducible ischemia or LCA involvement should undergo surgical revascularisation.

A longitudinal study of antibody responses to selected host antigens in rheumatic fever and rheumatic heart disease.

Introduction. Group A streptococci can trigger autoimmune responses that lead to acute rheumatic fever (ARF) and rheumatic heart disease (RHD).Gap Statement. Some autoantibodies generated in ARF/RHD target antigens in the S2 subfragment region of cardiac myosin. However, little is known about the kinetics of these antibodies during the disease process.Aim. To determine the antibody responses over time in patients and healthy controls against host tissue proteins - cardiac myosin and peptides from its S2 subfragment, tropomyosin, laminin and keratin.Methodology. We used enzyme-linked immunosorbent assays (ELISA) to determine antibody responses in: (1) healthy controls; (2) patients with streptococcal pharyngitis; (3) patients with ARF with carditis and (4) patients with RHD on penicillin prophylaxis.Results. We observed significantly higher antibody responses against extracellular proteins - laminin and keratin in pharyngitis group, patients with ARF and patients with RHD when compared to healthy controls. The antibody responses against intracellular proteins - cardiac myosin and tropomyosin were elevated only in the group of patients with ARF with active carditis. While the reactivity to S2 peptides S2-1-3, 8-11, 14, 16-18, 21-22 and 32 was higher in patients with ARF, the reactivity in the RHD group was high only against S2-1, 9, 11, 12 when compared to healthy controls. The reactivity against S2 peptides reduced as the disease condition stabilized in the ARF group whereas the reactivity remained unaltered in the RHD group. By contrast antibodies against laminin and keratin persisted in patients with RHD.Conclusion. Our findings of antibody responses against host proteins support the multistep hypothesis in the development of rheumatic carditis. The differential kinetics of serum antibody responses against S2 peptides may have potential use as markers of ongoing cardiac damage that can be used to monitor patients with ARF/RHD.

Long-term cardiac (valvulopathy) safety of cabergoline in prolactinoma.

BACKGROUND: Clinical relevance of association of cabergoline use for hyperprolactinemia and cardiac valvulopathy remains unclear. OBJECTIVE: The aim of the study was to determine the prevalence of valvular heart abnormalities in patients taking cabergoline for the treatment of prolactinoma and to explore any associations with the cumulative dose of drug used. DESIGN: A cross-sectional echocardiographic study was performed in patients who were receiving cabergoline therapy for prolactinoma. RESULTS: Hundred (61 females, 39 males) prolactinoma cases (81 macroprolactinoma and 19 microprolactinoma) were included in the study. The mean age at presentation was 33.9 ± 9.0 years (range: 16-58 years). The mean duration of treatment was 53.11 ± 43.15 months (range: 12-155 months). The mean cumulative dose was 308.6 ± 290.2 mg (range: 26-1196 mg; interquartile range: 104-416 mg). Mild mitral regurgitation was present in one patient (cumulative cabergoline dose 104 mg). Mild tricuspid regurgitation was present in another two patients (cumulative cabergoline dose 52 mg and 104 mg). Aortic and pulmonary valve functioning was normal in all the cases. There were no cases of significant valvular regurgitation (moderate to severe, Grade 3-4). None of the patients had morphological abnormalities such as thickening, calcification, and restricted mobility of any of the cardiac valves. CONCLUSION: Cabergoline appears to be safe in patients with prolactinoma up to the cumulative dose of ~300 mg. The screening for valvulopathy should be restricted to those with higher cumulative cabergoline exposure.

A rare endocrine cause of electrical storm - a case report.

Sheehan's syndrome, also called Simmond's syndrome, postpartum apoplexy, postpartum pituitary necrosis, and postpartum panhypopituitary syndrome, is the name given to postpartum hypopituitarism. The syndrome is caused by an infarction in the adenohypophysis, usually precipitated by massive uterine haemorrhage and hypovolemic shock during or after childbirth. Extensive destruction of pituitary cells results in varying degree of hypopituitarism. Acute loss of adenohypophysis function can be fatal without glucocorticoid and thyroid replacement therapy and survivors will require life time hormonal replacement therapy. Most cases present in the postpartum period with lactation failure or after months to years after the delivery. In many affected women, anterior pituitary dysfunction is not diagnosed for many years. Dyselectrolytemia is one of a common presentation in Sheehan's syndrome. Herein, we report a case of a 35-year old female with a history of obstetric hysterectomy 2 years ago in view of severe postpartum haemorrhage with history of failure of lactation and three episodes of syncope since last 1½ years and now presented with polymorphic ventricular tachycardia which required DC cardioversion. She was referred as a case of long QT syndrome. On investigating further, she had hypokalaemia secondary to hypopituitarism due to Sheehan's syndrome.

Prevalence, treatments and outcomes of coronary artery disease in Indians: A systematic review.

AIM: To conduct a systematic review on the prevalence, risk factors, treatments and outcomes of Coronary Artery Disease (CAD) in Indians. METHODS AND RESULTS: We conducted a systematic review of studies in Indians with CAD from Jan 1969 to Oct 2012. Initial search yielded 3885 studies and after review 288 observational studies were included. The prevalence of CAD in urban areas was 2.5%-12.6% and in rural areas, 1.4%-4.6%. The prevalence of risk factors was: smoking (8.9-40.5%), hypertension (13.1-36.9%) and diabetes mellitus (0.2-24.0%). The median time to reach hospital after an MI was 360 min. In hospital rates of drug use were: antiplatelets 68%-97.9%, beta blockers 47.3%-65.8% and ACEIs 27.8-56.8%. CONCLUSIONS: In this first systematic review of CAD in India, prevalence of risk factors is high, treatments delayed and use of evidence based treatments variable.

Cardiovascular Disease Performance Measures in the Outpatient Setting in India: Insights From the American College of Cardiology's PINNACLE India Quality Improvement Program (PIQIP).

BACKGROUND: India has a growing burden of cardiovascular disease (CVD), yet data on the quality of outpatient care for patients with coronary artery disease, heart failure, and atrial fibrillation in India are very limited. We collected data on performance measures for 68 196 unique patients from 10 Indian cardiology outpatient departments from January 1, 2011, to February 5, 2014, in the American College of Cardiology's PINNACLE (Practice Innovation and Clinical Excellence) India Quality Improvement Program (PIQIP). PIQIP is India's first national outpatient CVD quality-improvement program. METHODS AND RESULTS: In the PIQIP registry, we estimated the prevalence of CVD risk factors (hypertension, diabetes, dyslipidemia, and current tobacco use) and CVD among outpatients. We examined adherence with performance measures established by the American College of Cardiology, the American Heart Association, and the American Medical Association Physician Consortium for Performance Improvement for coronary artery disease, heart failure, and atrial fibrillation. There were a total of 68 196 patients (155 953 patient encounters), with a mean age of 50.6 years (SD 18.2 years). Hypertension was present in 29.7% of patients, followed by diabetes (14.9%), current tobacco use (7.6%), and dyslipidemia (6.5%). Coronary artery disease was present in 14.8%, heart failure was noted in 4.0%, and atrial fibrillation was present in 0.5% of patients. Among eligible patients, the reported use of medications was as follows: aspirin in 48.6%, clopidogrel in 37.1%, and statin-based lipid-lowering therapy in 50.6% of patients with coronary artery disease; RAAS (renin-angiotensin-aldosterone system) antagonist in 61.9% and beta-blockers in 58.1% of patients with heart failure; and oral anticoagulants in 37.0% of patients with atrial fibrillation. CONCLUSIONS: This pilot study, initiated to improve outpatient CVD care in India, presents our preliminary results and barriers to data collection and demonstrates that such an initiative is feasible in a resource-limited environment. In addition, we attempted to outline areas for further improvement in outpatient CVD care delivery in India.

Simultaneous transcatheter closure of ruptured sinus of Valsalva aneurysm and stent implantation for aortic coarctation.

Ruptured sinus of Valsalva aneurysm is a rare anomaly and an associated coarctation of aorta is even rarer. A combination of such defects is traditionally treated surgically. The surgery is necessarily staged and done through different approaches. We report successful simultaneous transcatheter treatment of both these defects performed in the same setting in an acutely ill adult male patient with a good intermediate-term follow-up.

Classical Cardiovascular Manifestations of Marfan Syndrome.

Presence of multiple cardiovascular manifestations of the Marfan syndrome in the same patient is not commonly encountered. We present a 49 year-old lady with this syndrome who presented with decompensated heart failure. Evaluation revealed presence of extensive Stanford type A aortic dissection alongwith severe aortic and mitral incompetence. However, the patient declined surgery and was discharged on medical management. At a year's follow-up, she had dyspnea of NYHA class II with persistent cardiovascular findings.

Anticoagulation with otamixaban and ischemic events in non-ST-segment elevation acute coronary syndromes: the TAO randomized clinical trial.

IMPORTANCE: The optimal anticoagulant for patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) managed with an invasive strategy remains controversial. OBJECTIVE: To compare the clinical efficacy and safety of otamixaban, a novel intravenous direct factor Xa inhibitor, with that of unfractionated heparin plus downstream eptifibatide in patients with NSTE-ACS undergoing a planned early invasive strategy. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, active-controlled superiority trial that enrolled 13,229 patients with NSTE-ACS and a planned early invasive strategy, at 568 active sites in 55 countries and conducted between April 2010 and February 2013. A planned interim analysis was conducted for otamixaban dose selection. INTERVENTIONS: Eligible participants were randomized to otamixaban (bolus and infusion, at 1 of 2 doses) or unfractionated heparin plus, at the time of percutaneous coronary intervention, eptifibatide. The otamixaban dose selected at interim analysis was an intravenous bolus of 0.080 mg/kg followed by an infusion of 0.140 mg/kg per hour. MAIN OUTCOMES AND MEASURES: The primary efficacy outcome was the composite of all-cause death or new myocardial infarction through day 7. RESULTS: Rates of the primary efficacy outcome were 5.5% (279 of 5105 patients) randomized to receive otamixaban and 5.7% (310 of 5466 patients) randomized to receive unfractionated heparin plus eptifibatide (adjusted relative risk, 0.99 [95% CI, 0.85-1.16]; P = .93). There were no differences for the secondary end points, including procedural thrombotic complications. The primary safety outcome of Thrombosis in Myocardial Infarction major or minor bleeding through day 7 was increased by otamixaban (3.1% vs 1.5%; relative risk, 2.13 [95% CI, 1.63-2.78]; P < .001). Results were consistent across prespecified subgroups. CONCLUSIONS AND RELEVANCE: Otamixaban did not reduce the rate of ischemic events relative to unfractionated heparin plus eptifibatide but did increase bleeding. These findings do not support the use of otamixaban for patients with NSTE-ACS undergoing planned early percutaneous coronary intervention. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01076764.

Supracardiac total anomalous pulmonary venous connection with bilateral (right and left) vertical veins and bilateral obstruction.

This report describes a rare form of obstructed supracardiac total anomalous pulmonary venous connection with two vertical veins (right and left) draining the right- and the left-sided pulmonary veins respectively without formation of a common chamber and with bilateral obstruction. Surgery for these patients is technically challenging due to the absence of a common chamber, and the prognosis is worse than for patients with a common chamber. Also, it is important to be aware of this entity so that an accurate noninvasive preoperative diagnosis by echocardiography alone without invasive cardiac catheterization is possible. This facilitates emergency surgical repair without delay, which is crucial to improvement of the outcome.