Randomized controlled trial of perhexiline on regression of left ventricular hypertrophy in patients with symptomatic hypertrophic cardiomyopathy (RESOLVE-HCM trial).

BACKGROUND: The presence and extent of left ventricular hypertrophy (LVH) is a major determinant of symptoms in patients with hypertrophic cardiomyopathy (HCM). There is increasing evidence to suggest that myocardial energetic impairment represents a central mechanism leading to LVH in HCM. There is currently a significant unmet need for disease-modifying therapy that regresses LVH in HCM patients. Perhexiline, a potent carnitine palmitoyl transferase-1 (CPT-1) inhibitor, improves myocardial energetics in HCM, and has the potential to reduce LVH in HCM. OBJECTIVE: The primary objective is to evaluate the effects of perhexiline treatment on the extent of LVH, in symptomatic HCM patients with at least moderate LVH. METHODS/DESIGN: RESOLVE-HCM is a prospective, multicenter double-blind placebo-controlled randomized trial enrolling symptomatic HCM patients with at least moderate LVH. Sixty patients will be randomized to receive either perhexiline or matching placebo. The primary endpoint is change in LVH, assessed utilizing cardiovascular magnetic resonance (CMR) imaging, after 12-months treatment with perhexiline. SUMMARY: RESOLVE-HCM will provide novel information on the utility of perhexiline in regression of LVH in symptomatic HCM patients. A positive result would lead to the design of a Phase 3 clinical trial addressing long-term effects of perhexiline on risk of heart failure and mortality in HCM patients.

Observational study of left ventricular global longitudinal strain in ST-segment elevation myocardial infarction patients with extended pharmaco-invasive strategy: A six months follow-up study.

AIMS AND OBJECTIVES: To evaluate left ventricular (LV) function by assessment of LV global longitudinal strain (GLS) in ST-segment elevation myocardial infarction (STEMI) patients who underwent delayed fibrinolysis and coronary intervention (extended pharmaco-invasive strategy), since LV function is one of the determinants of both immediate and long-term outcomes. METHODS: Prospective study of consecutive STEMI patients who underwent extended pharmaco-invasive strategy. The LV function was estimated using LV GLS at baseline and at 6 months. RESULTS: The study included eighty-seven STEMI patients who received delayed pharmaco-invasive therapy and coronary intervention. The primary aim of the study was to evaluate a change in LV function by assessment of GLS at 6 months as compared to baseline. Prior to PCI, LV ejection fraction was 48.08 ± 6.23% and GLS was -11.11 ± 2.99%. Procedural success was achieved in all patients. LV ejection fraction after 6 months of follow-up increased to 53.12 ± 5.61% and the GLS improved to -13.03 ± 3.06% In comparison to baseline, there was a significant improvement in both LV ejection fraction and GLS at 6 months of follow-up (P < .001).The cardiac mortality was 1.1% at 6 months. CONCLUSION: There is a significant improvement of LV function as assessed by GLS and ejection fraction at short-term follow-up. In a stable cohort of STEMI patients, extended pharmaco-invasive strategy is also a reasonable option if PCI cannot be performed within the first 24 hours, due to logistic and infrastructural constraints.

Intracardiac mass in chronic myeloid leukemia.

Chronic myeloid leukaemia (CML) is a neoplastic disorder of myeloid cell lines and is a less aggressive disease compared to acute myeloid leukemia (AML). Although cardiovascular complications are not uncommon, intracardiac thrombosis in CML is rarely reported. Herein, we report a case of CML presenting with an intracardiac thrombus attached to the posterior mitral leaflet, and subsequently resulting in peripheral embolization.

Incidence and predictors of target lesion failure in a multiethnic Asian population receiving the SYNERGY coronary stent: A prospective all-comers registry.

OBJECTIVES: To evaluate the target lesion failure (TLF) rate of the SYNERGY stent in all-comers, multiethnic Asian population. BACKGROUND: Currently, most drug eluting stents deliver anti-proliferative drugs from a durable polymer which is associated with a risk of late stent thrombosis. The novel everolimus-eluting, platinum chromium SYNERGY stent is coated with a bioabsorbable abluminal polymer that resolves within 4 months. METHODS: This was a prospective, single center registry of consecutive patients treated with the SYNERGY stent between December 2012 and April 2015. The primary outcome was the incidence of TLF, defined as the combination of cardiac death, target vessel myocardial infarction, or clinically driven target lesion revascularization (TLR) at 1 year. RESULTS: A total of 807 patients received the SYNERGY stent during the study period. One-year clinical outcome data was available for 765 patients (94.8%) and were considered for statistical analysis. The mean age was 60.7 ± 10.8 years, and 83.4% were males. Patients with acute myocardial infarction consisted of 50.3% (ST-segment elevation myocardial infarction: 23.0%, Non-ST-segment elevation myocardial infarction: 27.3%) of the study population. The treated lesions were complex (ACC/AHA type B2/C: 72.7%). The primary end point of TLF at 1 year was 5.8%. Rates of cardiac mortality, target vessel myocardial infarction, and TLR were 4.2, 1.0, and 1.3%, respectively, at 1 year. Predictors of the incidence and time to early TLF were female gender, Malay ethnicity, diabetes mellitus, acute myocardial infarction at presentation, a prior history of coronary artery bypass surgery and the presence of lesion calcification. The incidence of definite stent thrombosis was 0.4% at 1 year. CONCLUSIONS: In this registry, the use of the SYNERGY stent was associated with low rates of TLF at 1 year.

Prosthetic mitral valve thrombosis, malfunction, and paroxysmal mitral regurgitation.

Intermittent dysfunction of mechanical mitral valve prosthesis is an uncommon condition. It carries serious clinical implications if unrecognized. Here, we present a case of a 28-year-old female with a history of rheumatic multivalvular disease, for which she had undergone double valve replacement and tricuspid annuloplasty. Six months later, she presented with heart failure. Clinical examination revealed intermittent loss of closing clicks followed by a pansystolic murmur at the apex, suggestive of mitral prosthetic valve dysfunction. We highlight the echocardiographic findings of paroxysmal mitral valvular regurgitation secondary to prosthetic valve malfunction secondary to prosthetic valve thrombosis.

Percutaneous stenting of interrupted aortic arch to treat compressive myelopathy.

Neurological complications of coarctation of aorta include spontaneous SAH, intracerebral hemorrhage, and cerebral abscess. Interrupted aortic arch (IAA) present as compressive myelopathy is not known. We describe an adult male presenting to neurology department with progressive paraparesis and was detected to have IAA with intraspinal collaterals causing compressive myelopathy. He was successfully treated with percutaneous stenting of IAA with dramatic improvement in paraparesis. © 2014 Wiley Periodicals, Inc.

Acute severe mitral regurgitation following balloon mitral valvotomy: echocardiographic features, operative findings, and outcome in 50 surgical cases.

OBJECTIVE: To analyze the echocardiographic and operative findings with respect to mitral valve anatomy in individuals undergoing emergency surgery for acute severe mitral regurgitation (MR) following balloon mitral valvotomy (BMV). In addition, the clinical profile and outcomes are highlighted. BACKGROUND: Acute severe MR is a major complication of BMV. There are only a few reports which have studied the echocardiographic and operative findings in this setting. In addition, optimal timing of surgery is uncertain. METHODS: Prospective study of 50 consecutive patients undergoing emergency mitral valve replacement (MVR) for acute severe MR following BMV. RESULTS: In 3855 patients who underwent BMV, acute severe MR developed in 50 cases (1.3%) and was referred for emergency MVR. Hypotension (72%), hypoxia (64%), orthopnea (14%), and pulmonary edema (12%) were the clinical manifestations. Severe MR was secondary to anterior mitral leaflet tear in 36 cases (72%), paracommisural tear with annular involvement in seven cases (14%), posterior mitral leaflet tear in five cases (10%) and chordal tear in two cases (4%). The correlation between two-dimensional transthoracic echocardiography (2D-TTE) and operative finding for mitral valve calcification was found to be strong (r = 0.862), in contrast to submitral fusion, where it was found to be moderate (r = 0.536). In-hospital mortality was 12%. Mortality was higher in patients whose time to surgery was ≥24 hr when compared to those who underwent MVR within 24 hr (P < 0.001). CONCLUSIONS: Hypotension and hypoxia are the predominant manifestations of acute severe MR following BMV. Anterior mitral leaflet tear is the most common etiology for severe MR. 2D-TTE underestimated the severity of submitral disease. Early MVR (<24 hr) is recommended for optimal outcome.

Utility of cardiovascular magnetic resonance in patients with stable troponin elevation.

AIMS: Cardiovascular magnetic resonance (CMR) imaging has a potential role in the evaluation of symptomatic patients with stable troponin elevation; however, its utility remains unexplored. We sought to determine the incremental diagnostic value of CMR in this unique cohort and assess the long-term clinical outcomes. METHODS AND RESULTS: Two hundred twenty-five consecutive patients presenting with cardiac chest pain/dyspnoea, stable troponin elevation, and undergoing CMR assessment were identified retrospectively from registry database. The study cohort was prospectively followed for major adverse cardiac events (MACEs) (defined as composite of all-cause mortality and cardiovascular readmissions). The primary outcome measure was the diagnostic utility of CMR, i.e. percentage of patients for whom CMR identified the cause of stable troponin elevation. Secondary outcome measures included the incremental value of CMR and occurrence of MACE. CMR was able to identify the cause for stable troponin elevation in 160 (71%) patients. A normal CMR was identified in 17% and an inconclusive CMR in 12% of the patients. CMR changed the referral diagnosis in 59 (26%) patients. Utilizing a baseline prediction model (pre-CMR referral diagnosis), the net reclassification index was 0.11 and integrated discriminatory improvement index measured 0.33 following CMR. Over a median follow-up of 4.3 years (interquartile range 2.8-6.3), 72 (32%) patients experienced MACE. CONCLUSION: CMR identified a cause for stable troponin elevation in 7 of 10 cases, and a new diagnosis was evident in 1 of 4 cases. CMR improved the net reclassification of patients with stable troponin elevation.

Long-term clinical outcomes in patients with a working diagnosis of myocardial infarction with non-obstructed coronary arteries (MINOCA) assessed by cardiovascular magnetic resonance imaging.

BACKGROUND: Myocardial infarction with non-obstructed coronary arteries (MINOCA) is a distinct entity among patients presenting with troponin-positive acute chest pain. We have previously reported on the incremental diagnostic capability of cardiovascular magnetic resonance (CMR) in this cohort. There is paucity of evidence on the long-term (> 5 years) clinical outcomes of these patients as graded by their acute CMR diagnosis. METHODS AND RESULTS: A total of 229 patients with a working diagnosis of MINOCA who underwent CMR assessment during the acute admission (2010-2017) were prospectively studied. The primary endpoint was major adverse cardiac events (MACE) defined as a composite of all-cause mortality and cardiovascular readmissions, identified from hospital and primary care records. CMR performed at a median of 6 days (IQR 2, 8) from presentation provided a diagnosis in 85% of the patients (38% myocarditis, 28% acute myocardial infarction and 19% Takotsubo cardiomyopathy). Over a median follow-up of 7.1 years (IQR 3.7, 8.2), 56 (24%) patients experienced a MACE. We found a strong association between CMR diagnosis and MACE (log rank 30.47, p < 0.001). In multivariate analysis, age (hazard ratio = 1.07; 95% confidence interval = 1.05, 1.10; p < 0.001) and CMR diagnosis of acute myocardial infarction (hazard ratio = 8.87; 95% confidence interval = 2.58, 30.4; p = 0.001) were independent predictors of MACE. CONCLUSIONS: In a large cohort of patients with a working diagnosis of MINOCA, one in four suffer a MACE during long-term clinical follow-up. CMR diagnosis of acute myocardial infarction and age were significant predictors of MACE even in the absence of significant coronary artery obstruction.

Isolated left ventricular noncompaction mimicking ventricular mass.

Isolated left ventricular noncompaction is an inherited cardiomyopathy characterized by multiple prominent trabeculations with deep intertrabecular recesses. The diagnosis is often missed because echocardiography poses inherent problems of poor echo window in assessment of the LV apex, which is most commonly involved in noncompaction. We report a case in which conventional 2D echocardiography failed to demonstrate multiple prominent trabeculations. Contrast echocardiography confirmed the presence of multiple trabeculations with deep intertrabecular recesses. This report emphasizes the importance of contrast echocardiography in the diagnosis of ventricular noncompaction.

Cardiac Amyloidosis: The Importance of Surveillance in a Patient With an Initial Negative Cardiac Biopsy.

Cardiac amyloidosis is a progressive disorder and is sometimes difficult to diagnose even when suspected in the appropriate clinical setting. We present an interesting case of rapidly progressive light-chain cardiac amyloidosis and highlights the importance of close monitoring even when the initial biopsy and imaging findings are not pathognomonic for amyloidosis. (Level of Difficulty: Beginner.).

"Incidence, clinical and angiographic characteristics, management and outcomes of coronary artery perforation at a high volume cardiac care center during percutaneous coronary intervention".

AIMS: To study the incidence, clinical and angiographic characteristics, management and outcomes of coronary artery perforation (CAP) during percutaneous coronary intervention (PCI) at a high volume center in South-east Asia. METHODS: Data from patients who had CAP during PCI from January 2016 to December 2019 at our center were collected. Clinical features, angiographic and procedural characteristics, their management and outcomes were analyzed retrospectively. RESULTS: A total of 40,696 patients underwent PCI during the study period and the incidence of CAP was 0.13% (n = 51). Mean age was 60.0 ± 10.8 years and 69% were males. CAP cases involved complex type B2/C lesions in 73%, calcified lesions in 58%, and chronic total occlusions in 25%. Majority of patients presented as acute coronary syndrome (65%) and STEMI was the most frequent indication for PCI (33%). Most of the CAPs were Ellis type II (33%) and III (55%). CAP most frequently occurred during post dilation (n = 20) and wire manipulation (n = 17). Majority were treated by prolonged balloon inflation (53%) and covered stents (33%). Pericardiocentesis was required in 19 patients to alleviate tamponade. In one patient coil embolisation was done and two patients required bail-out emergency cardiac surgery. Periprocedural myocardial infarction occurred in 6% and in-hospital mortality was 10%. All-cause mortality accrued to 14% at 30 days and 16% at 6 months. CONCLUSION: Although incidence of CAP in contemporary interventional practice remains low, the morbidity and mortality are considerable. Early recognition and management strategies tailored to the severity of perforation play a key role in achieving better outcomes.

Hemopericardium Following Transseptal Puncture During Balloon Mitral Valvotomy: Management Strategies and Outcomes.

BACKGROUND: Hemopericardium is a major complication of balloon mitral valvotomy (BMV). Only a few studies are available to address this issue following transseptal access. In addition, the management strategy regarding completion of BMV is uncertain. OBJECTIVE: We sought to determine the incidence of hemopericardium complicating transseptal puncture during BMV. In addition, the management strategy adopted and outcomes are highlighted. METHODS: This prospective study included 29 consecutive patients who developed hemopericardium following transseptal access during BMV. RESULTS: Out of 1424 patients who underwent BMV, hemopericardium developed in 29 patients following transseptal access (2.0%). The mean age of the study cohort was 36.9 ± 13.7 years and 82.8% were women. A second transseptal puncture was done and BMV was completed in 26 patients (89.6%). An acceptable hemodynamic result was obtained in 22 patients (84.6%). Six patients (20.7%) underwent emergency surgery for hemopericardium. The sites of perforation were inferior vena cava-right atrial junction in 4 cases, left atrial posterior wall in 1 case, and left atrial appendage in 1 case. In addition to repair of the perforation, a total of 2 patients underwent mitral valve replacement and 1 patient underwent open mitral commissurotomy. The in-hospital mortality rate was 6.9%. CONCLUSIONS: The incidence of hemopericardium complicating transseptal access during BMV was 2.0%, and was associated with a mortality rate of 6.9%. BMV can be safely performed in the same sitting with a second transseptal puncture, in patients with a favorable valve morphology. Surgical intervention can be reserved for a subset of patients with persistent pericardial collection.

Left ventricular ischemia in pre-capillary pulmonary hypertension: a cardiovascular magnetic resonance study.

BACKGROUND: Prognosis in pulmonary arterial hypertension (PAH) is largely dependent on right ventricular (RV) function. However, recent studies have suggested the presence of left ventricular (LV) dysfunction in PAH patients. The potential role of LV ischemia, as a contributor to progressive LV dysfunction, has not been systematically studied in PAH. We aim to assess the presence and extent of LV myocardial ischemia in patients with known PH and without obstructive coronary artery disease (CAD), using oxygen-sensitive (OS) cardiovascular magnetic resonance (CMR) and stress/rest CMR T1 mapping. METHODS: We prospectively recruited 28 patients with right heart catheter-proven PH and no significant CAD, 8 patients with known CAD and 11 normal age-matched controls (NC). OS-CMR images were acquired using a T2* sequence and T1 maps were acquired using Shortened Modified Look-Locker Inversion recovery (ShMOLLI) at rest and adenosine-induced stress vasodilatation; ΔOS-CMR signal intensity (SI) index (stress/rest SI) and ΔT1 reactivity (stress-rest/rest T1 mapping) were calculated. RESULTS: Global LV ΔOS SI index was significantly lower in PH patients compared with controls (11.1%±6.7% vs. 20.5%±10.5%, P=0.016), as was ΔT1 reactivity (5.2%±4.5% vs. 8.0%±2.9%, P=0.047). The ischemic segments of CAD patients had comparable ΔOS SI (10.3%±6.4% vs. 11.1%±6.7%, P=0.773) to PH patients, but lower ΔT1 reactivity (1.1%±4.2% vs. 5.2%±4.5%, P=0.036). CONCLUSIONS: Decreased OS-CMR SI and T1 reactivity signify the presence of impaired myocardial oxygenation and vasodilatory response in PH patients. Given their unobstructed epicardial coronary arteries, this is likely secondary to coronary microvascular dysfunction (CMD).

Selective use of drug-eluting stents in high-risk versus bare metal stents in low-risk patients according to predefined criteria confers similar four-year long-term clinical outcomes.

Aims: The aim of the study was to evaluate the long-term outcomes following selective implantation of drug-eluting stents (DES) in patients at high risk of restenosis versus bare metal stents (BMS) in low-risk patients, according to predefined criteria. Methods and results: Patients who underwent elective percutaneous coronary intervention (PCI) between May 2002 and April 2004 were enrolled in this retrospective, single-centre study. All patients received a BMS while undergoing PCI, unless they fulfilled at least two entry criteria that warranted DES usage. The study endpoints were major adverse cardiac events (MACE), comprising death, myocardial infarction, stent thrombosis (ST), and target vessel revascularisation (TVR), at four years between the DES and BMS groups. A total of 1,250 patients were enrolled in the study, among whom 1,095 (88%) received BMS and the rest received DES. At four years, there was no difference in the cumulative incidence of MACE: death (4.5% in DES vs. 5.8% in BMS, p=0.531), myocardial infarction (2.6% in DES vs. 3.1% in BMS, p=0.722), TVR (9.7% in DES vs. 7.9% in BMS, p=0.461), and ST (1.9% in DES vs. 0.8% in BMS, p=0.183). The event-free survival rate at four years was similar in the two groups (87.1% in DES vs. 86.1% in BMS; p=0.741). Conclusions: In elective PCI, a strategy of selective use of DES in patients at high risk of restenosis based on predefined criteria confers the same favourable long-term clinical outcomes as BMS in low-risk patients.

A propensity score-matched comparison of biodegradable polymer vs second-generation durable polymer drug-eluting stents in a real-world population.

AIMS: The safety and efficacy of BP-DES compared to second-generation DP-DES remain unclear in the real-world setting. We compared the clinical outcomes of biodegradable polymer drug-eluting stents (BP-DES) with second-generation durable polymer drug-eluting stents (DP-DES) in an all-comer percutaneous coronary intervention (PCI) registry. METHODS/RESULTS: The study included a cohort of 1065 patients treated with either BP-DES or DP-DES from January 2009 through October 2015. Propensity score matching was performed to account for potential confounders and produced 497 matched pairs of patients. The primary endpoint was target lesion failure (TLF) at one-year follow-up. The rates of TLF were comparable between BP-DES and DP-DES (8.7% vs 9.1%, P = .823) at 1 year. The rates of stent thrombosis at 30 days (0.4% vs 0.4%, P = 1.00) and 1 year (0.8% vs 0.8%, P = 1.00) did not differ between BP-DES and DP-DES. There were no significant differences in other clinical outcomes including target vessel failure (8.9% vs 9.5%, P = .741), in-stent restenosis (1.8% vs 1.0%, P = .282), and cardiac death (6.4% vs 7.4%, P = .533) at 1 year. Multivariate cox regression analysis showed that the risk of TLF at one-year did not differ significantly between BP-DES and DP-DES (hazard ratio 0.94, P = .763). CONCLUSIONS: Efficacy and safety of BP-DES were not better than DP-DES at one-year follow-up.

Cost-effectiveness analysis of biodegradable polymer versus durable polymer drug-eluting stents incorporating real-world evidence.

AIM: Compared with second-generation durable polymer drug-eluting stents (DP-DES), the cost-effectiveness of biodegradable polymer drug-eluting stents (BP-DES) remains unclear in the real-world setting. We assessed the cost-effectiveness of BP-DES in patients with coronary artery disease undergoing percutaneous coronary intervention (PCI). METHODS: We developed a decision-analytic model to compare the cost-effectiveness of BP-DES to DP-DES over 1 year and 5 years from healthcare payer perspective. Relative treatment effects during the first year post-PCI were obtained from a real-world population analysis while clinical event risks in the subsequent 4 years were derived from a meta-analysis of published studies. RESULTS: At 1 year, based on the clinical data analysis of 497 propensity-score matched pairs of patients, BP-DES were associated with an incremental cost-effectiveness ratio (ICER) of USD20 503 per quality-adjusted life-year (QALY) gained. At 5 years, BP-DES yielded an ICER of USD4062 per QALY gained. At the willingness-to-pay threshold of USD50 400 (one gross domestic product per capita in Singapore in 2015), BP-DES were cost-effective. Sensitivity analysis showed that the cost of stents had a significant impact on the cost-effectiveness of BP-DES. Threshold analysis demonstrated that if the cost difference between BP-DES and DP-DES exceeded USD493, BP-DES would not be cost-effective in patients with 1 year of follow-up. CONCLUSIONS: Biodegradable polymer drug-eluting stents were cost-effective compared with DP-DES in patients with coronary artery disease at 1 year and 5 years after PCI. It is worth noting that the cost of stents had a significant impact on the findings.