In an observational case series of 80 patients who underwent heart transplant using hearts from hepatitis C (HCV)–positive donors, it has been shown that short-term (30-day) and long-term survival (1-year) of recipients testing positive for HCV exceeds 90% and is not significantly different to that of patients receiving heart transplants from HCV negative donors.

Results of the study titled “Expanding Heart Transplant in the Era of Direct-Acting Antiviral Therapy for Hepatitis C” were published in JAMA Cardiology. Dr. Kelly H. Schlendorf, MD (Vanderbilt University Medical Center, Nashville, Tennessee) and colleagues analyzed data from 80 patients (median age, 54.5 years; 71% men; 69% white) who underwent heart transplants with HCV-positive donors between September 2016 and April 2019. The authors found that the median active wait-list time from the time patients consented to accept HCV-positive donor hearts was 4 days (interquartile range [IQR], 1-18) versus 28 days (IQR, 6-168) for patients before providing consent. This was significantly lower than the national reported median wait times between 70 and 535 days.

The investigators categorized HCV positive donors into two groups: viremia positive and viremia negative (as determined by nucleic acid amplification test [NAAT]). Those with presence of viremia, a total of 70 donors had 95.7% transmission rate of HCV to their recipients, while none of the 10 recipients of hearts from NAT-negative donors developed infection (transmission rate, 0%). In patients testing positive with donor-derived HCV (ddHCV) 30-day and 1-year patient survival rates were 92.5% and 90.4%, respectively. A total of 6 (8.5%) patients with ddHCV died (5 due to primary allograft rejection and 1 due to development of pulmonary embolism). In addition, in the ddHCV cohort, 10 (14.9%) had acute cellular rejection and 1 patient (1.5%) had a single antibody-mediated graft rejection. Length of hospital stay and readmissions of ddHCV recipients were not significantly different from those who received heart transplants from HCV negative donors (median length of stay 15 days vs. 17 days, respectively; P = .79 for difference). Similarly, rates of coronary allograft vasculopathy in recepients also did not reveal any difference regardless of HCV positivity in donors. However, the authors noted that the recipients of transplants from HCV-positive donors exhibited significantly higher rates of severe primary graft dysfunction than recipients of transplants from HCV-negative donors (13.7% vs 3.1%; P = .002). Recipients suffering from ddHCV received direct anti-virals combinations using either Ledipasvir-sofosbuvir (90 mg-400 mg), Sofosbuvir-velpatasvir (400 mg-100 mg) or Glecaprevir-pibrentasvir (100 mg-40 mg) for 12 weeks. It was found that sustained virologic response at 12 weeks was 100% for ddHCV positive recepients.

Extended periods of wait-times for patients requiring heart transplants leads to significant morbidity and mortality. It has been shown that atleast 10% of patients requiring heart transplants die due to long wait-list times and the numbers get worse as wait times increase further. Results from the current study indicate that in the current era of direct acting anti-virals for HepC treatment, heart transplants from HepC positive donors is a viable option for expansion of donor pools and reduce wait list times for those awaiting transplants. Nevertheless, results from this study need to be interpreted with caution due to its limitations. The study was done at a single-center with surrounding municipalities that were affected by opioid crisis with an increased load of HepC donors, which may fail to account for geographical differences that exist in other areas.

A cross-sectional observational study enrolling 223 patients with 3-vessel coronary artery disease, has shown that compared to conventional invasive coronary angiography, a noninvasive physiology assessment using fractional flow reserve CT scanning (FFRCT or multi-slice CT scanning) changed heart team’s treatment decision-making and procedural planning in 1/5th of the patients.

The SYNTAX III REVOLUTION Trial was a randomized, multi-center study which randomized two heart teams to make a treatment decision between percutaneous coronary interventions (PCI) and coronary artery bypass grafting (CABG) using either coronary computed tomography angiography (CTA) or conventional invasive angiography while blinded to the other imaging modality. The study included patients with complex coronary artery disease, defined as, left main (isolated, or associated with 1, 2 or 3 vessel disease) or de novo 3-vessel coronary artery disease (DS ≥50%), who were able to receive cardiac CT with a multi-slice CT scanner. Coronary CTA was performed with the GE Revolution CT scanner that has a nominal spatial resolution of 230 microns along the X–Y planes, a rotational speed of 0.28 s, and a Z-plane coverage of 16 cm enabling to image the heart in one heartbeat. Patients with concomitant atrial fibrillation, cardiac valve disease and prior history of PCI or CABG were excluded from the study. The primary outcome was the inter-rater agreement (assessed by Cohen’s Kappa Kappa; a value of 0.82) on revascularization strategy of two heart teams by employing the use of either an “Angio-first” algorithm or a “CT First” algorithm 1 to 2 weeks after patient enrollment. The addition of FFRCT changed the treatment decision in 7% of the patients and modified selection of vessels for revascularization in 12%. With conventional angiography as a reference, FFRCT assessment resulted in reclassification of 14% of patients from intermediate and high to low SYNTAX score tertile.

The American and European guidelines recommend a heart team based approach for the decision-making process regarding the revascularization strategy and recommend the evaluation of the anatomical complexity using the SYNTAX score. Patients with SYNTAX scores >34 have been found to do much better with bypass surgery than those with lower SYNTAX scores. The SYNTAX scores can be divided into three tertiles. Higher scores signify complex conditions and indicate greatest risks to patients undergoing PCI. Calculation of the SYNTAX score takes into account complex lesions including bifurcations, chronic total occlusions, thrombus, calcification, and small diffuse disease with a total of 11 measures of lesion complexity. The score ranges from 0 to greater than 60 in very complex coronary anatomy.

Previously validated SYNTAX II score utilizes SYNTAX I score and then combines it with clinical prognostic variables such as age, creatinine clearance, gender, left main vessel involvement, left ventricular ejection fraction, chronic obstructive pulmonary disease (COPD) and peripheral vascular disease (PVD) in order to guide selection between PCI and CABG for patients with multivessel coronary disease. The results of the SYNTAX III Trial suggest the potential feasibility of a treatment decision-making and planning that stems from a non-invasive imaging modality and clinical information.

A randomized parallel-group trial comparing intensive LDL-C lowering to modest lowering for prevention of major adverse cardiovascular events (MACE) in patients with recent ischemic stroke in the setting of atherosclerosis has shown that an aggressive LDL-C reduction strategy with a goal of < 70mg/dl is superior to modest reduction approach which targets a range of 90-110 mg/dl.

Results of the Treat Stroke to Target Trial (TST trial) which enrolled 2860 patients (32% females) with a median follow-up of 3.5 years were presented by Dr. Amarenco (Department of Neurology and Stroke Center, Bichat Hospital, France) at AHA 2019 and simultaneously published in The New England Journal of Medicine.

Patients with established atherosclerotic cardiovascular disease (ASCVD) and ischemic stroke within the past 3 months or transient ischemic stroke (TIA) within the past 15 days (modified Rankin score of 0-3) were randomized in 1:1 fashion to statin therapy with either a goal LDL-C of < 70 mg/dl (n =1430) or 90-110 mg/dl (n = 1430).

The primary efficacy endpoint of the trial was composite of MACE (nonfatal cerebral infarction or stroke of undetermined origin, nonfatal myocardial infarction, hospitalization for unstable angina followed by urgent coronary-artery revascularization, TIA treated with urgent carotid revascularization, or CV death). The primary outcome occurred in 8.5% of patients assigned to the group with intensive LDL lowering compared to 10.9% of patients in the modest control approach (adjusted hazard ratio, 0.78; 95% confidence interval [CI], 0.61 to 0.98; P=0.04). Mean LDL-C levels at baseline were 135 mg/dl for both groups and at 3.5 years for the intensive vs. modest treatment groups were 65 vs. 96 mg/dl (p < 0.05). Secondary outcomes were occurrence of MI, need for urgent revascularization, all-cause mortality, intracranial hemorrhage, and newly diagnosed diabetes mellitus. Rates of intracranial hemorrhage (1.3% vs. 0.9% [p > 0.05]) and new-onset diabetes mellitus (7.2% vs. 5.7% [p > 0.05]) were numerically higher with more aggressive control, but not statistically significant.

The present study highlights the clinical benefit obtained by a tighter control of plasma LDL levels for secondary prevention of stroke. Previously, the SPARCL trial showed that in patients who have had a stroke within the prior one to six months without coronary artery disease, treatment with 80 mg atorvastatin led to a lower incidence of recurrent MACE including fatal and nonfatal strokes. In the Heart Protection Study (HPS), simvastatin 40mg did not show benefit in secondary stroke protection, but in HPS, patients were enrolled after a mean of 4.3 years of having a cerebrovascular accident, whereas the greatest risk for recurrent strokes resides within the first year of suffering from a cerebrovascular accident.  Though findings from the current TST trial are in line with the SPARCL trial in terms of reduction of recurrent MACE, the SPARCL trial saw an increase in the incidence of hemorrhagic strokes in the treatment arm, while the present TST clinical trial revealed no rise in hemorrhagic stroke rates in patients despite achieving more aggressive reductions in their serum LDL-C levels.

The authors ask the readers to interpret the results of the TST trial while considering the fact that the study was stopped prematurely due to insufficient funding at 3.5 years and did not reach the goal of 385 events, instead, 277 primary events were recorded for the analysis. In addition, secondary endpoints could not be tested due to the failure of hierarchical clustering of endpoints.

An expanded analysis of 231 patients from the GALILEO trial comparing rivaroxaban-aspirin based anti-thrombotic therapy with clopidogrel-aspirin based dual anti-platelet therapy post transcatheter aortic valve replacement (TAVR), has shown that the rivaroxaban based regimen protects from valve leaflet motion abnormalities. The rivaroxaban based strategy led to decreased prosthetic valve leaflet thickening and motion reduction following TAVR performed for severe aortic valve stenosis. Continue reading →

A single center study that included 187 patients who presented with angina-like chest pain and nonobstructive coronary arteries on diagnostic angiography, has shown that co-existence of high microvascular resistance index (IMR) and vasospasm is associated with an increased incidence of major adverse cardiovascular events (MACE – defined as cardiac death, nonfatal myocardial infarction, and hospitalizations). Rho-kinase activation thought to underlie mechanisms leading to high IMR in this patient population.
The 187 patients included in the study had a median follow-up of 893 days. Continue reading →

A registry-based cohort study including 72,660 Medicare patients with and without atrial fibrillation (AF) who underwent non-apical transcatheter aortic valve replacement (TAVR) from 2014 to 2016, has shown that, TAVR patients with new-onset AF have the highest rate of all-cause mortality (32%) compared to patients with pre-existing or no AF (23.3% and 12.8%, respectively). New-onset AF was also associated with an increased risk of bleeding, stroke and heart failure (HF) hospitalizations.

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A randomized, double blind, placebo-controlled, phase II clinical trial studying the effect of a novel protein proprotein convertase subtilisin/kexin type 9 (PCSK9) synthesis inhibitor (inclisiran) on serum low density lipoprotein cholesterol (LDL-C) levels has shown that twice a year subcutaneous injections of inclisiran leads to a sustained dose-dependent reduction in serum LDL-C levels over a period of 1 year.

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A randomized, double-blinded, placebo-controlled trial which enrolled 7119 high risk  patients with coronary artery disease who had undergone recent percutaneous coronary intervention (PCI) has shown that, after 3 months of dual anti-platelet therapy (DAPT) using a P2Y12 receptor blocker (ticagrelor) and aspirin, continuing secondary prevention with a single anti-platelet therapy (SAPT) with ticagrelor alone reduces bleeding as compared to extended DAPT.

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Results from a phase-IIIb, open-label, multi-center, randomized clinical trial comparing the safety of dual anti-thrombotic therapy (DAT) with triple anti-thrombotic therapy (TAT) for patients with atrial fibrillation who have undergone recent (4 hours – 5 days) percutaneous coronary intervention (PCI), have shown that the DAT regimen (Edoxaban plus a P2Y12 inhibitor) is non-inferior to Vitamin K antagonist(VKA) plus a P2Y12 inhibitor and aspirin or TAT regimen.

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A randomized, mutilcenter, placebo-controlled, phase 3 clinical trial which enrolled 676 patients (aged 18-80 years) presenting to the ER with acute ischemic stroke assessed  the efficacy and safety of transcranial ultrasound (US) as an adjunctive therapy to intravenous tissue plasminogen activator (IV-tPA, administered over 60 minutes) treatment (CLOTBUST-ER trial). The results from the trial, which was stopped due to futility show that although the use of sonothrombolysis was feasible and most likely safe, no clinical benefit was seen at 90 days. Compared with the control group, the adjusted cOR for an improvement in modified Rankin Scale score (mRSC) at 90 days in the intervention group was 1.05 (95% CI 0.77–1.45; p=0.74). Andrei Alexandrov, MD (University of Tennessee Health Science Center, Memphis), and colleagues reported in the April 2019 issue of the Lancet Neurology. Continue reading →

A randomized multi-center trial which enrolled 1000 patients from 71 centers around the world has shown that in patients with severe aortic stenosis who are at low surgical risk, the rate of the composite of death, stroke, or rehospitalization at 1 year is significantly lower with transcatheter aortic valve replacement (TAVR) than with surgery. Continue reading →

The US food and drug Administration (FDA) has recently been conducting an investigation on voluntary recalls of multiple generic angiotensin II receptor blocker (ARB) drug products used to treat high blood pressure and heart failure. The recalls initiated in July 2018 and continue to date due to the presence of Nitrosamine impurities, including N-Nitrosodimethylamine (NDMA) and N-Nitrosodiethylamine (NDEA), which are potential human carcinogens in different ARB products. Last week, AurobindoPharma USA notified that it is expanding its recall to include 38 more lots of valsartan and amlodipine/valsartan tablets due to objectionable levels of N-Nitrosodiethylamine (NDEA). This was later followed by an expanded voluntary recall of losartan potassium produced by Hetero Labs (India) when they were found to be contaminated by N-Nitroso-N-methyl-4-aminobutyric acid (NMBA). Camber Pharmaceuticals called back 87 lots of losartan potassium tablets (25 mg, 50 mg and 100 mg), 114 lots of losartan potassium or losartan potassium/hydrochlorothiazide tablets, and one lot of losartan potassium/hydrochlorothiazide tablets. Continue reading →

A multi-center randomized, double blind, placebo-controlled, parallel group clinical trial has shown that among patients with acute ST-elevation myocardial infarction (STEMI) presenting within 6 hours of symptoms, adjunctive low-dose intracoronary alteplase given after reperfusion via primary percutaneous intervention does not reduce microvascular obstruction. Continue reading →

A population-based cohort study has shown that patients with a higher serum cholesterol efflux capacity, the capacity of HDL particles to mediate cholesterol efflux from macrophages, have a marked decrease in all-cause mortality as compared to patients with a lower serum cholesterol efflux capacity. Continue reading →

Results of a multi-center, randomized clinical trial which enrolled 894 patients with heart failure (HF) with reduced ejection fraction (EF ≤40%) published in the most recent issue of the Journal of the American College of Cardiology (JACC) have shown that management, using NT-ProBNP-guided optimal medical therapy, has higher total costs and fails to show superior efficacy in improving quality of life (QoL) outcomes compared to usual care (titration of guideline-recommended therapy to doses established in pivotal clinical trials).

The GUIDE-IT (GUIDing Evidence Based Therapy Using Biomarker Intensified Treatment in Heart Failure) trial planned to prospectively enroll 1100 patients from 45 clinical sites in the United States and Canada. After a scheduled review by the DSMB, the study was stopped for lack of efficacy of the biomarker-guided strategy. The patients included in the study presented with chronic HF and an EF of ≤40%; these subjects were randomly assigned in a 1:1 fashion to an NT-proBNP-guided treatment strategy (n=446) or usual care (n=448). Patients in the NT-proBNP- guided strategy received medical therapy with a goal of achieving a NT-proBNP level <1000 pg/ml. Structured evaluations performed at baseline and 3, 6, 12, and 24 months post-randomization were employed to collect and compare data on quality of life (QoL). The Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score and the Duke Activity Status Index (DASI) were used to stratify pre-specified QoL measures. In addition, researchers examined the costs associated with either treatment strategy in 735 US patients. The results showed that both the KCCQ and the DASI improved over the first 6 months ( 11-point improvement in the 4 KCCQ composite scales which included physical limitations, total symptoms, QoL, and social limitations), but no evidence was found for a strategy-related difference (mean difference [biomarker-guided usual care] at 24 months of follow-up, 2.0 for DASI [95% confidence interval (CI): 1.3 to 5.3] and 1.1 for KCCQ [95% CI: 3.7 to 5.9]). Albeit the lack of strategy-related difference, both treatment arms did show improvements in KCCQ and DASI scores overall. Total winsorized costs (to reduce the effect of possibly false outliers) averaged $5,919 higher in the biomarker-guided strategy (95% CI: $1,795 + $13,602) over 15-month median follow-up.

Previous trials have revealed various effective management strategies for HF patients that lead to symptomatic relief (primarily dyspnea) and improve prognosis but other major symptoms such as fatigue and exercise intolerance have not been well correlated with either central measures of cardiac performance or measures of patient-reported QoL. Indeed, most of the clinical trials of effective medical therapies in HF that included QoL measurement showed small or no changes in QoL. NT‐proBNP has emerged as a powerful biomarker in various cardiovascular diseases and serves to provide strong and independent prognostic information in patients with heart failure. The investigators of the GUIDE-IT trial aimed to study whether the attempt to achieve a sufficiently low NT-proBNP level would affect QoL either beneficially or adversely. The investigators concluded that they found no evidence of a QoL effect associated with randomization to the strategy of NT-proBNP– guided therapy. In 735 patients enrolled in the United States, medical costs were increased in the biomarker-guided arm, primarily due to extra hospital-based care.

The limitations of the study included early termination with less follow-up time than was planned for in the trial design, secondly the unblinded nature of the analyses may have contributed to the lack of benefit seen in the biomarker-guided arm. Thirdly, both groups had more frequent medical contacts related to study participation compared to standard of care.

Results from a multi-center, randomized, double-blind, double dummy, parallel group clinical trial which enrolled 881 patients with heart failure (HF) with reduced ejection fraction (HFrEF-left ventricular ejection fraction of 40% or less) have shown superior efficacy of Sacubitril–Valsartan combination (Entresto; Novartis) in reducing N-terminal pro-B-type natriuretic peptide compared to Enalapril alone. The patients were hospitalized for acute decompensation of HF, and treatment with Sacubitril–Valsartan achieved a greater reduction in N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations without any significant offsetting serious adverse events. Findings from the trial were presented at the 2018 AHA Scientific Session and simultaneously published in the New England Journal of Medicine (NEJM). Continue reading →

A new prospective observational study of 38 patients suffering from myocardial infarction with non-obstructive coronary artery disease (MINOCA) with the use of optical coherence tomography (OCT) and complementary cardiac magnetic resonance imaging (CMR) shows plaque disruption and thrombus account for one-fourth and one-fifth of MINOCA, respectively. Both plaque disruption and thrombosis were repeatedly found in coronary vessels supplying the infarct-related territory as confirmed by CMR. This is the first prospective study that successfully employed the use of OCT along with complementary CMR for studying the basic mechanisms leading to MINOCA suggesting that OCT may aid in deciphering the basic underpinnings of this not so rare type of myocardial infarction (MI).

MINOCA is increasingly being seen in clinical practice. Prior studies have served as a major effort to understand the pathophysiology of this presentation, which may aid in effective secondary prevention in this patient population. Several questions exist due to the heterogeneous nature of patients who suffer from MINOCA. Given this background, Opolski (Department of Interventional Cardiology and Angiology, Institute of Cardiology, Warsaw, Poland) and colleagues prospectively enrolled 38 patients (mean age 62 years; 55% women) with MI but <50 % stenosis on angiography (maximal diameter stenosis of 35%) in order to identify the mechanisms that lead to MINOCA. On OCT, nine patients (24%) showed signs of plaque disruption and seven (18%) had evidence of coronary thrombus. A per-lesion analysis of CMR results further demonstrated that, compared with non-infarct-related arteries, infarct-related arteries displayed more plaque disruption (40% vs 6%; P = 0.02), thrombus (50% vs 4%; P = 0.014), and thin-cap fibroatheroma (70% vs 30%; P = 0.03). Moreover, the investigators found that subjects with plaque disruption albeit non-significant tended to have numerically higher rates of ischemic late gadolinium contrast enhancement (LGE) on CMR than subjects without plaque disruption (50% vs. 13%, respectively; p = 0.053).

Utilization of OCT

Optical coherence tomography (OCT) is a high-resolution (10 to 15 mm) intracoronary imaging modality that employs the use of coherent light waves for precise assessment of the integrity of the atheromatous fibrous cap. This allows for visualizing plaques and thrombosis that may be otherwise missed on conventional angiography. In this study, the investigators aimed to perform OCT imaging in at least the coronary vessel that was suspected to be the culprit vessel (based on electrocardiography [EKG], echocardiography, and angiography).

Evaluation of Myocardial Injury on CMR

In this study, myocardial edema was evaluated as an area of high T2 signal intensity on a segmental basis (Left ventricle segments were defined by American Heart Association 17-segment model). The presence and pattern of late gadolinium enhancement (LGE) were determined for each segment and divided into subendocardial, subepicardial, midwall, or transmural. LGE in the subendocardial and transmural distributions were considered ischemic. Correlation between the coronary artery distribution and myocardial segments with LGE of ischemic origin served as a source of identification of infarct-related artery.

Limitations

The study has its limitations since it was a small, single-center, and observational study. In addition, loss of eligible patients due to logistical problems and withdrawals of informed consent gives rise to selection bias. Furthermore, the investigators failed to perform 3-vessel OCT imaging in all patients, which could have resulted in a lower proportion of patients with plaque disruption and/or thrombus (specifically owing to a lower rate of OCT in the right coronary artery).

Results from an open-label, multi-center, 2×2 factorial design randomized trial powered for equivalence, comparing the self-expanding Corevalve Evolut R valve to balloon expandable Edwards Sapien 3 valve, have shown that the two valves were equivalent to each other in terms of decreasing all-cause mortality, stroke, moderate or severe prosthetic valve regurgitation, and permanent pacemaker implantation (p=0.02). Trial results presented at the 2018 TCTMD conference held at San Diego, California, also showed equivalence in a comparison between general anesthesia vs local anesthesia (with conscious sedation) in terms of decreasing all-cause mortality, stroke, myocardial infarction, infection requiring antibiotic treatment, and acute kidney injury (p=0.02). Continue reading →

A randomized global, prospective, multi-center, single-blind trial comparing the Eluvia paclitaxel-eluting stent (Boston Scientific) to  Zilver PTX paclitaxel-eluting stent (Cook Medical) has shown that the Eluvia stent outperformed Zilver in terms of efficacy, which was defined as primary patency at 12 months. These findings, published in The Lancet, were presented by Dr. William Gray at the annual TCT 2018 conference held in San Diego today. Continue reading →

 In a randomized multi-center clinical trial that enrolled more than 700 patients with multi-vessel coronary artery disease and acute myocardial infarction (MI) with cardiogenic shock, it was shown that percutaneous coronary intervention (PCI) of the culprit lesion only (with the option of staged revascularization of nonculprit lesions) was associated with better clinical outcomes compared to immediate multi-vessel PCI. It was found that at 30 days, there was a 9.5% absolute reduction in the rate of the primary endpoint of death or renal replacement therapy in patients randomized to culprit-lesion only revascularization. Previously DANAMI-3-PRIMULTI, PRAMI, and CvLPRIT trials have suggested that there may be a benefit to complete revascularization but those studies did not enroll patients with hemodynamic instability or cardiogenic shock. Consequently, this led to the inclusion of immediate multi-vessel PCI in the 2015 ACC/AHA/SCAI STEMI guidelines as a Class II-b recommendation (can be considered). Continue reading →