|Year : 2015 | Volume
| Issue : 1 | Page : 87-90
Sunil K Verma
Department of Cardiology, AIIMS, New Delhi, India
|Date of Web Publication||22-May-2015|
Dr. Sunil K Verma
Department of Cardiology, AIIMS, New Delhi
Source of Support: None, Conflict of Interest: None
In the year 2014, there were certain remarkable trials that have changed the practice of cardiology and beyond that these tried to explained some long awaited unanswered questions. Like SIMPLICITY HTN-3 trial clearly explained the uselessness of renal denervation therapy in systemic hypertension. PARADIGM-HF trial provided positive data that may be useful to enrich the basket of medical treatment with a new drug LCZ 696 after a long time. Another important meta-analysis in heart failure questioned the status of beta blockers as standard therapy to improve prognosis in patients with concomitant heart failure and atrial fibrillation . In myocardial infraction , CvLPRIT trial supported the concept of complete revascularization at the time of primary PCI and TASTE trials failed to show expected benefit of thrombus aspiration in acute MI. FFR got more strength from FAME 2 trial. Another important question that was addressed in SECURITY trial was optimal duration of DAPT after second generation DES implantation. One year follow-up results of ABSORB II suggested that bioresorbable scaffolds are currently facing problem of stent thrombosis that might be taken care in near future with improvement in strut technology. Successful use of "Heart in a box" machine provided a major thrust for cardiac transplantation. SEARCH-AF evaluated the efficacy of a novel mobile health technology in the real world to screen for atrial fibrillation (now called as life style disease). A Meta-analysis provided a more comprehensive picture of the new oral anticoagulants as a therapeutic option in atrial fibrillation. Positive results for trans catheter pm-VSD closure in paediatric population were also demonstrated by a randomized controlled trial. Role of corticosteroids in tubercular pericarditis also got the answer in a trial published in 2014.
Keywords: Dual antiplatelet therapy, drug eluting stent, fractional flow reserve, coronary artery disease
|How to cite this article:|
Verma SK. Cardiology update. J Pract Cardiovasc Sci 2015;1:87-90
In this section we have tried to bring all the major trials and development in the field of cardiology under one umbrella.
| Systemic Hypertension|| |
All the hopes and enthusiasms related to the successful treatment of one of the major diseases, Systemic Hypertension that is the culprit of a large number of cardiac, cerebral and vascular mortality and morbidity all across the world, got a full stop with the declaration of the results of the SIMPLICITY HTN-3  trial. This was a prospective, single-blind, randomized, sham-controlled trial. A total of 535 patients underwent randomization. This trial of renal denervation for resistant hypertension did not reveal a significant reduction of systolic blood pressure in patients with resistant hypertension 6 months after renal-artery denervation as compared with a sham control.
| Heart Failure|| |
Heart failure with reduced ejection fraction has underwent remarkable improvement over past few decades with demonstration of substantially improved quality and expectancy of life with medications (AEC-I, ARBs, β blockers, diuretics and mineralocorticoid receptor antagonists) and cardiac devices (CRT & CRT-D). The medication arm can now be enriched with addition of a novel drug LCZ 696 which is an inhibitor of both angiotensin receptor and neprilysin. PARADIGM-HF  trial demonstrated a clear significant benefit of LCZ 696 (at doses of 200 mg BD) compared to enalapril (at a dose of 10 mg BD) in addition to recommended therapy in a randomly assigned 8442 patients with class II, III or IV heart failure and an EF of 40% or less. LCZ 696 is a combination of neprilysin (a neutral endopeptidase) inhibitor sacubitril and the ARB valsartan. At a mean of 27 months follow-up, the primary outcome of cardiovascular death and hospitalization for heart failure had occurred in 21.8% of patients in the LCZ696 group versus 26.5% in the enalapril group (P < 0.0001). In addition LCZ696 significantly reduced incidence of the individual endpoints of total death, cardiovascular death, and hospitalization for heart failure, and decreased the symptoms of physical limitations of heart failure. It is very useful that PARADIGM-HF demonstrated the superiority of LCZ 696 to enalapril in reducing the risk of death and or hospitalization for heart failure. However there are certain questions that need to be answered. One that this therapy is to be used in place of ACE-I and it is unlikely that it will provide an incremental benefit when used in combination with ACE-I as previous experience in VALIANT trial. Secondly, in PARADIGM-HF trial, about 60% cases were of ICMP and about 43% of patients were having H/O MI, but this group needs further evaluation before considering acceptability. Lastly the safety issues of symptomatic hypotension, renal impairment, hyperkalemia, cough and angioedema are still there as with ACE-I.
An important meta-analysis  questioned the role of beta blockers in subgroup of patients of heart failure having atrial fibrillation. Data included in this meta-analysis was from ten randomised controlled trials of the comparison of β blockers versus placebo in heart failure. The presence of sinus rhythm or atrial fibrillation was ascertained from the baseline electrocardiograph. The primary outcome was all-cause mortality. 18,254 patients were assessed, and of these 13,946 (76%) had sinus rhythm and 3066 (17%) had atrial fibrillation at baseline. Crude death rates over a mean follow-up of 1.5 years were 16% (2237 of 13,945) in patients with sinus rhythm and 21% (633 of 3064) in patients with atrial fibrillation. β-blocker therapy led to a significant reduction in all-cause mortality in patients with sinus rhythm (P < 0.001), but not in patients with atrial fibrillation (P = 0.73). The lack of efficacy for the primary outcome was noted in all subgroups of atrial fibrillation, including age, sex, left ventricular ejection fraction, NYHA class, heart rate, and baseline medical therapy. The recommendation of this meta-analysis was that, β blockers should not be used preferentially over other rate-control medications and not regarded as standard therapy to improve prognosis in patients with concomitant heart failure and atrial fibrillation.
| Coronary Artery Disease|| |
The debate regarding complete revascularization during primary PCI got strength by the CvLPRIT  (Complete Versus Lesion Only PRimary-PCI Trial) trial. Results from the CvLPRIT found that patients with ST-segment elevation myocardial infarction (STEMI) undergoing complete revascularization had better outcomes and experienced fewer major adverse cardiac events compared with those who had only "culprit" artery revascularization. These results reinforce data from another trial, PRAMI (Preventive Angioplasty in Myocardial Infarction), which showed percutaneous coronary intervention (PCI) of all coronary arteries with >50% angiographic narrowing may improve outcomes. Questions do remain about the exact timing of nonculprit artery PCI (i.e., at time of primary PCI or later during the index hospitalization), and whether certain patients benefit versus others.
The fascinating concept of retrieval of thrombus in acute STEMI during primary PCI failed again.
This time TASTE  (Thrombus Aspiration in ST-Elevation Myocardial Infarction in Scandinavia) trial assessed the benefit of routine thrombus aspiration at the time of primary PCI for STEMI. They reported no survival with routine thrombus aspiration or any reduction in a combined endpoint of death, re-hospitalization for myocardial infarction, or stent thrombosis at one year.
FFR(Fractional flow reserve) got more place in interventional management of stable coronary artery disease with the results of FAME 2  (Fractional flow reserve versus Angiography for Multivessel Evaluation 2) trial. FAME 2 compared contemporary PCI plus medical treatment (MT) to MT alone in patients with stable CAD. 'Contemporary' refers to PCI guided by FFR and using second generation drug-eluting stents (DES). The predefined primary endpoint was a composite of death from any cause, nonfatal myocardial infarction (MI), or unplanned hospitalisation leading to urgent revascularisation during the first two years. In contrast to most previous trials in patients with stable CAD, only those with a stenosis able to induce myocardial ischaemia as assessed by an FFR value ≤0.80 were included. These patients were randomised to either PCI + MT (n = 447) or to MT alone (n = 441). The remaining 332 patients were not randomised but followed-up in a registry and treated with MT. The trial concluded that in patients with stable CAD and at least one haemodynamically significant stenosis, FFR-guided PCI plus medical therapy is associated with a 61% reduction in major adverse cardiac events after two years.
Anti platelet therapy
One of important controversy regarding optimal duration of dual anti platelet therapy following coronary angioplasty was addressed by SECURITY  trial. This trial was designed to establish the optimal duration of DAPT following 2 nd generation DES implantation. Non inferiority of 6 months versus 12 months DAPT in patients undergoing PCI with 2 nd generation DES was tested. This a was 1:1 randomized, multicenter, and international, investigator driven study comprising of about 1400 patients with a diagnosis of stable or unstable angina or documented silent ischemia undergoing revascularization with at least one 2 nd generation DES. This was a low risk patient population group. Randomization was done to receive DAPT for 6 months (n = 682) vs. 12 months (n = 717). Non-inferiority hypothesis was confirmed (P = <0.05) for primary end points(composite of cardiac death, MI, stroke, definite or probable stent thrombosis or BARC type 3 to 5 bleeding at 12 months). Moreover, no difference was observed in the occurrence of secondary end points at 12 months. Also no differences were present in definite or probable stent thrombosis at 12 months and between 12 and 24 months of follow-up. So, in a low risk patient of stable or unstable angina receiving at least one 2 nd generation DES, the non-inferiority of hypothesis (6 months vs. 12 months) appears accepted regarding the incidence of cardiac death, MI, stroke, definite/probable stent thrombosis and BRAC type 3 or 5 bleeding at 12 months.
ABSORB II  trial presented the first randomized data on everolimus-eluting bioresorbable scaffold. The trial investigated 501 subjects who were randomized two to one either the everolimus-eluting bioresorbable scaffold (Absorb, n = 335) or the everolimus-eluting metallic stent (Xience, n = 166). Although the trial is planned for a 5 year follow-up, the one year data on secondary clinical end points were released in the view of rapid adoption of this novel treatment modality. None of the patients in Xience group developed definite or probable stent thrombosis over one year period. In Absorb group, 2 patients developed definite scaffold thrombosis- 1st patient at 0-1 day (acute) which received LAD-Diagonal bifurcation scaffolding, 2nd patient at 2-30 days (sub-acute) which received two long 28 mm non-overlapping scaffold in LAD. One probable scaffold thrombosis occurred late (31-365 days). At one year, DoCE (cardiac death, TV-MI & TLR, Absorb 4.8% Vs Xience 3.0%, P = 0.35), PoCE (all death, all MI and all revascularization, Absorb 7.3% Vs Xience 9.1%, P = 0.47) and their components were similar between two arms. Angiography and IVUS analysis demonstrated that acute gain was significantly lower in the Absorb arm than in the Xience arm. Exercise performance and angina status demonstrated comparable results in both groups. One hypothesis generating observation was a difference in the nitrate use at 6 months and at 12 months in favour of Absorb arm.
Hence the one year follow-up results draw attention towards scaffold thrombosis probably in overlapping scaffolds (either at bifurcation or non-bifurcation point). It might be the technological improvement in the strut design will eliminated this problem in near future.
St Vincent Hospital, Sydney performed cardiac transplantation  using donor hearts that stopped beating about 20 minutes. It was the series of a first successful cardiac transplantations utilizing "Heart in a box" machine (a machine that revived the heart by pumping warm nutrient rich oxygenated blood into it). Instead of cold cardioplegia warm blood was utilized for the first time for preservation of heart in cardiac transplantation. The preservative solution for the machine was developed by Victor chang cardiac research institute.
Cardiovascular and neurological outcomes scan be reduced when we attempt to diagnose atrial fibrillation early in its natural history. SEARCH-AF  trial, in which the AliveCor Heart Monitor, a single lead ECG device built into an iPhone case, was used to screen 1,000 patients in community pharmacies for atrial fibrillation. It was a pretty well done and carefully crafted study to evaluate the efficacy of a novel mobile health technology in the real world. A total of 996 patients were screened, and the following were found: (1) 87 patients were identified to have atrial fibrillation or undetermined rhythm on the single-lead tracing, (2) 58 of those patients had prior known atrial fibrillation; 15 were "new" diagnoses of atrial fibrillation, (3) 10 of the 15 "new" patients had no prior history and were actually new diagnoses; 5 had remote atrial fibrillation presumed to be converted permanently back to sinus, (4) 14 of the 15 "new" atrial fibrillation patients had follow up and 9 of them ended up on anticoagulation, (5) For the 5 with follow up who did not end up on anticoagulation, 2 from the new group were in sinus on follow up. The benefits of anticoagulation for atrial fibrillation in stroke prevention are well defined. With newer generation anticoagulants, having patients on therapy will likely become even less costly and burdensome. Strategies that help diagnose silent atrial fibrillation and get appropriate patients on therapy before a stroke can have a major impact.
Newer oral anticoagulants
In the field of newer oral anticoagulants, a meta-analysis  answered some questions. The meta analysis comparing the efficacy and safety of newer oral anticoagulants with warfarin in patients with atrial fibrillation included the 71,683 participants of RE-LY, ROCKET AF, ARISTOTLE, and ENGAGE AF-TIMI 48 trials. This meta-analysis is the first to include data for all four new oral anticoagulants studied in the pivotal phase 3 clinical trials for stroke prevention or systemic embolic events in patients with atrial fibrillation The main outcomes were stroke and systemic embolic events, ischemic stroke, haemorrhagic stroke, all-cause mortality, myocardial infarction, major bleeding, intracranial haemorrhage, and gastrointestinal bleeding. 42,411 participants received a new oral anticoagulant and 29,272 participants received warfarin. New oral anticoagulants had a favourable risk-benefit profile, with significant reductions in stroke, intracranial haemorrhage, and mortality, and with similar major bleeding as for warfarin, but increased gastrointestinal bleeding. The relative efficacy and safety of new oral anticoagulants was consistent across a wide range of patients. These findings offer clinicians a more comprehensive picture of the new oral anticoagulants as a therapeutic option to reduce the risk of stroke in this patient population.
Congenital heart disease
Surgical closure of pmVSD is a well-established therapy but requires open-heart surgery with cardiopulmonary bypass. Although the transcatheter approach for pm VSD closure is associated with significant incidence of complete atrioventricular block, it may provide a less invasive alternative. Critical comparison of the safety and efficacy of the 2 interventions was evaluated in a prospective, randomized, controlled trial.  229 children with pmVSD were randomly assigned to surgical or transcatheter intervention. Shanghai pm VSD occluder was used in the intervention arm. Clinical, laboratory, procedural, and follow-up data over a 2-year period were compared. Transcatheter device closure and surgical repair were effective interventions with excellent midterm results for treating pm VSD in children. Transcatheter device closure has a lower incidence of myocardial injury, less blood transfused, faster recovery, shorter hospital stay, and lower medical expenses.
Whether corticosteroids are beneficial for patients with tuberculous pericarditis has been controversial. Using a 2-by-2 factorial design, this trial  randomly assigned 1400 adults with definite or probable tuberculous pericarditis to either prednisolone or placebo for 6 weeks and to either M. indicus pranii or placebo, administered in five injections over the course of 3 months in South Africa. Two thirds of the participants had concomitant human immunodeficiency virus (HIV) infection. The primary efficacy outcome was a composite of death, cardiac tamponade requiring pericardiocentesis, or constrictive pericarditis. There was no significant difference in the primary outcome between patients who received prednisolone and those who received placebo or between those who received M. indicus pranii immunotherapy and those who received placebo. Prednisolone therapy, as compared with placebo, was associated with significant reductions in the incidence of constrictive pericarditis and hospitalization. Both prednisolone and M. indicus pranii, each as compared with placebo, were associated with a significant increase in the incidence of cancer owing mainly to an increase in HIV-associated cancer. Hence the trial concluded that in patients with tuberculous pericarditis, neither prednisolone nor M. indicus pranii had a significant effect on the composite of death, cardiac tamponade requiring pericardiocentesis, or constrictive pericarditis.
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