Sodium-Glucose Cotransporter-2 Inhibitors and Primary Prevention of Atherosclerotic Cardiovascular Disease: A Meta-Analysis of Randomized Trials and Systematic Review.

Background Sodium-glucose cotransporter-2 (SGLT2) inhibitors reduce atherosclerotic cardiovascular disease (ASCVD) events in patients with prior ASCVD and type 2 diabetes; however, this benefit is uncertain in patients without established ASCVD. Methods and Results Large-scale cardiovascular outcome randomized controlled trials or their prespecified subgroup analyses were selected, evaluating SGLT2 inhibitors versus placebo for primary prevention of ASCVD (inception, March 2023). The primary outcome was atherosclerotic major adverse cardiovascular events (MACEs), which was a composite of cardiovascular mortality, myocardial infarction, and stroke. The secondary outcomes were individual components of MACEs and all-cause mortality. The outcomes were reported as random-effect relative risk (RR) with a 95% CI. This analysis, comprising 23 987 patients enrolled in 5 randomized controlled trials with a mean follow-up duration of ≈135 weeks, found no significant reduction in atherosclerotic MACEs with SGLT2 inhibitors in comparison to placebo (RR, 0.85 [95% CI, 0.71-1.01]; P=0.07; I2=44). There were no significant differences in cardiovascular mortality (RR, 0.93 [95% CI, 0.77-1.14]; P=0.50; I2=0), myocardial infarction (RR, 0.88 [95% CI, 0.69-1.11]; P=0.28; I2=23), and stroke (RR, 0.84 [95% CI, 0.62-1.16]; P=0.29; I2=46). SGLT2 inhibitors significantly improved all-cause mortality (RR, 0.85 [95% CI, 0.72-1.0]; P=0.04; I2=23). On subgroup analyses, the use of SGLT2 inhibitors led to significant reductions in MACEs (RR, 0.74 [95% CI, 0.61-0.89]; P=0.001), myocardial infarction (RR, 0.67 [95% CI, 0.47-0.97]; P=0.03), and stroke (RR, 0.61 [95% CI, 0.41-0.91]; P=0.01) primarily in patients with chronic kidney disease along with type 2 diabetes, whereas these benefits were not observed in patients with type 2 diabetes without chronic kidney disease. Conclusions SGLT2 inhibitors significantly reduced atherosclerotic MACEs in subjects having both chronic kidney disease and type 2 diabetes without established ASCVD.

Perioperative Evaluation of Infective Endocarditis Via Multimodality Imaging for the Surgical Management of Aortic Root Abscess.

Infective endocarditis (IE) is an infection of the endothelium of the heart, that typically affects heart valves. While echocardiography remains crucial in the diagnosis and management of IE, multimodality cardiac imaging helps obtain additional information for the management of complex cases. Alternative imaging modalities such as computed tomography (CT), computed tomography angiography (CTA), and magnetic resonance imaging (MRI) are playing an increasing role in the diagnosis and management of IE, especially for patients with prosthetic valve endocarditis (PVE). Here we present a case of a 60-year-old Caucasian male who was diagnosed with IE, complicated by aortic root abscess, and multiorgan failure. In this challenging case, multimodality cardiac imaging helped in the precise understanding of the extent of endocarditis, cannulation strategy, and direct the course of the surgical procedure that resulted in successful patient management.

A case report of a massive cardiac intimal sarcoma manifesting as syncope during a stress test.

BACKGROUND: Syncope has many aetiologies but from a cardiac standpoint, if arrhythmogenic and ischaemic causes are not present, obstructive lesions should be considered. Cardiac spindle cell sarcomas are incredibly rare and difficult to cure. CASE SUMMARY: A 62-year-old man presented for exercise stress test and had a syncopal episode on the treadmill. He was found to have a massive mass obstructing the transmitral flow. Patient was taken to the operating room and the mass was resected successfully. Histopathological confirmation revealed the mass to be a cardiac intimal sarcoma. Patient was initiated on a trial regimen of doxorubin, ifosfamide, and mesna. DISCUSSION: Cardiac intimal sarcomas are aggressive cancers and are difficult to treat; there are no established treatment guidelines. They can lead to obstruction of blood flow through the cardiac chambers. From a cardiac perspective, without arrhythmogenic and ischaemic causes of syncope, obstructive lesions should be considered.

Sequential His bundle and left ventricular pacing for cardiac resynchronization.

INTRODUCTION: Fusion of left ventricular pacing with intrinsic conduction provides superior resynchronization compared to biventricular pacing. His bundle pacing (HBP) preserves intrinsic conduction and allows for constant fusion with left ventricular pacing. This study evaluated sequential His bundle and left ventricular pacing for cardiac resynchronization therapy (CRT). METHODS: In patients referred for CRT, sequential His bundle and left ventricular pacing was performed when HBP did not correct the QRS. At implant, QRS duration and area were compared between biventricular pacing and His bundle and left ventricular pacing. Devices were programmed for His and left ventricular pacing. Functional status and echocardiography were evaluated in follow up. RESULTS: Twenty-one patients, seven female, 70.7 ± 9.9 years, 57% with nonischemic cardiomyopathy were included. Baseline QRS duration was 170 ± 21 ms and was 157 ± 16 ms with HBP. Biventricular pacing resulted in a QRS duration of 141 ± 15 ms and decreased to 110 ± 14 ms with His bundle and left ventricular pacing (p < .0005). His bundle and left ventricular pacing resulted in a smaller paced QRS area (38.5 ± 22.6 µVs) compared to biventricular pacing (67.5 ± 24.0 µVs) and baseline (78.1 ± 28.1 µVs; p < .0005). Left ventricular ejection fraction increased from 27.6 ± 6.4% to 41.1 ± 12.5 (at 25 mean months, p = .001) and functional class improved from 3.1 ± 0.5 to 2.1 ± 0.8 (at mean 32 months, p < .001). CONCLUSIONS: Sequential His bundle and left ventricular pacing results in superior electrical synchrony in patients with indication for CRT when HBP does not correct the QRS and resulted in promising clinical and echocardiographic response rates.

Embolization of aortic valve leaflet during valve-in-valve transcatheter aortic valve implantation: a case report.

BACKGROUND: Aortic stenosis (AS) is one of the most common valvular disorders worldwide. An increasing number of transcatheter aortic valve implantation (TAVI) procedures are being performed yearly for managing AS. This, along with the occurrence of common complications, makes timely diagnosis essential to manage rare complications and improve patient outcomes. CASE SUMMARY: We present a case of a 77-year-old Caucasian male with severe AS with a dysfunctional bioprosthetic valve following previous surgical valve replacement. During valve-in-valve TAVI, we noted bioprosthetic valve leaflet avulsion and embolization causing a major vascular occlusion that resulted in vascular insufficiency of the left lower extremity. This condition was managed successfully via immediate diagnosis using transoesophageal echocardiogram, angiogram, and vascular surgical intervention for retrieving the embolized valve to re-establish circulation. DISCUSSION: To our knowledge, this is the first case of aortic valve leaflet embolization during TAVI resulting in significant vascular insufficiency. Vascular complications are common during TAVI. However, not all vascular complications are the same. Our case highlights an embolic vascular complication from an avulsed prosthetic material during a challenging valve-in-valve TAVI procedure.

Angioplasty Balloon Entrapped Fully Inflated and Detached Within the Left Main Coronary Artery.

Described is a complication of rescue left main coronary stenting due to threatened left main closure following a "valve in valve" TAVR procedure. Left main stent post dilatation with a NC Trek balloon was complicated by a failure to deflate the balloon. The patient spiraled into cardiogenic shock and was stabilized by an intra-aortic balloon pump. Attempts to withdraw the balloon resulted in shearing of the balloon off the shaft. Parallel wiring and sequential balloon dilatations allowed left main bifurcation stenting while crushing the inflated balloon underneath the stent's struts. Follow up of 13 months was uneventful. The management of entrapped inflated coronary balloon is reviewed.

Evaluating Association Between Coronary Calcifications Visualized During Invasive Coronary Angiography With Total Mortality.

BACKGROUND: High calcium score is independently associated with a greater cardiac event rate. Using a large database of patients who underwent coronary angiography for clinical reasons, we evaluated the association between reported degree of coronary calcification with mortality and baseline risk factors. METHODS: Using angiographic data of 1917 patients from 1993 to 1997, we studied any association between the locations of coronary calcium that were seen during coronary angiography with coronary artery risk factors. Furthermore, we correlated the locations of calcium with all cause mortality. RESULTS: A total of 1917 patients who underwent cardiac catheterization from 1993 to 1997 were studied. Total mortality was 22.9%. There was no association between the classic coronary risk factors (history of hypertension, hyperlipidemia, smoking, diabetes mellitus and family history) or race (White, Black, Hispanic, and Asian) with the occurrence of angiographic visible calcium in any location. Furthermore, we did not find any association between the locations of coronary calcium with all cause mortality. (All cause mortality occurred in 21.8% of patients with left main calcification vs. 23.3%, P = 0.63, in 24.6% of patients with left anterior descending artery calcification vs. 22.7%, P = 0.48, in 25.6% of patients with circumflex calcification vs. 23.1%, P = 0.52, in 25.7% of right coronary calcification vs. 22.7%, P = 0.47, in 24.6 of any coronary calcification vs. 22.5%, P = 0.4). CONCLUSIONS: Race, coronary risk factors, and all cause mortality are not associated with angiographic documented coronary calcification in any location in patients undergoing diagnostic coronary angiography.

Meta-analysis of Temporal and Surgical Risk Dependent Associations With Outcomes After Transcatheter Versus Surgical Aortic Valve Implantation.

Temporal and surgical risk dependent associations with clinical outcomes in patients receiving transcatheter versus surgical aortic valve implantation (TAVI vs SAVI) are uncertain. In this meta-analysis, 7 randomized controlled trials (7,771 patients) were included to investigate trends in outcomes in TAVI versus SAVI up to 5 years, and variation in outcomes with respect to low-, intermediate-, and high-surgical risk of the patients up to 1 year. Estimates were calculated as random effects hazard ratios (HRs) with 95% confidence intervals (CI). All-cause mortality was similar in TAVI and SAVI at 30 days (HR 0.81, 95% CI 0.55 to 1.21, p = 0.31), 1 year (HR 0.97, 95% CI 0.89 to 1.06, p = 0.49), 2 years (HR 0.96, 95 CI 0.85 to 1.09, p = 0.54), and 5 years (HR 1.04, 95% CI 0.89 to 1.21, p = 0.62). Cardiac mortality, myocardial infarction and stroke were similar in both interventions up to 5 years. TAVI was associated with lower risk of atrial fibrillation, but higher risk of vascular complications, pacemaker implantation, and paravalvular leak up to 5 years. The lower risks of major bleeding and acute kidney injury with TAVI versus SAVI were limited to 1 and 2 years, respectively. Compared with SAVI, TAVI was superior in reducing all-cause mortality in low surgical risk patients at 30 days only, whereas TAVI was noninferior to SAVI in intermediate- and high-risk patients at 30 days and across all risks at 1 year. In conclusion, TAVI was noninferior to SAVI in terms of mortality, myocardial infarction, and stroke up to 5 years. TAVI improved survival versus SAVI in low-risk patients at 30 days.

Higher Prevalence of Abnormal Electrocardigrams (ECG) in African Americans Undergoing Screening ECG and Echocardiography.

BACKGROUND: African American (AA) has higher prevalence of abnormal electrocardigrams (ECG) in general population. However, the degree of these abnormalities in a healthy population undergoing screening echocardiography is not known. The goal of this study was to evaluate the prevalence of ECG abnormalities reported during screening echocardiography based on race. METHOD: The Anthony Bates Foundation has been performing screening across the United States for the prevention of sudden death since 2001. We evaluated a total of 633 participants with documented race and ECG for the presence of any abnormalities. RESULTS: The age of the study population ranged between 6 and 75 years old. The prevalence of abnormal ECG in AA participant was 20.7% (12/58) versus 6.6% (38/578) in other races [odds ratio (OR), 3.70; confidence interval (CI), 1.8-7.58; P < 0.001]. Using multivariate analysis adjusting for age, sex, body mass index, left ventricular hypertrophy, and hypertension (systolic blood pressure >140 and diastolic blood pressure of >90), AA race remained independently associated with abnormal ECG (OR, 2.58; CI, 1.12-5.97; P = 0.02). Limiting our study only to teenagers (age, 13-19 years), AA race remained significantly associated with higher prevalence of ECG abnormalities [23.1% (12/58) of teenage AA had abnormal ECG vs. 7.5% (24/321) of other teenage races; OR, 3.71; CI, 1.36-10.11; P = 0.006]. After excluding benign ECG abnormalities such as sinus bradycardia and early repolarization, AA race remained significantly associated with higher prevalence of abnormal ECG (16.7% vs. 7.3%; OR, 2.52; CI, 0.998-6.39; P = 0.054). CONCLUSIONS: The prevalence of abnormal ECG is higher in AA race independent of echocardiographic abnormalities or demographics. However, some of these abnormalities appear to be related to sinus bradycardia and early repolarization.

Association of Lowering Low-Density Lipoprotein Cholesterol With Contemporary Lipid-Lowering Therapies and Risk of Diabetes Mellitus: A Systematic Review and Meta-Analysis.

Background The relationship between lowering LDL (low-density lipoprotein) cholesterol with contemporary lipid-lowering therapies and incident diabetes mellitus ( DM ) remains uncertain. Methods and Results Thirty-three randomized controlled trials (21 of statins, 12 of PCSK9 [proprotein convertase subtilisin/kexin type 9] inhibitors, and 0 of ezetimibe) were selected using Medline , Embase, and the Cochrane Central Register of Controlled Trials (inception through November 15, 2018). A total of 163 688 nondiabetic patients were randomly assigned to more intensive (83 123 patients) or less intensive (80 565 patients) lipid-lowering therapy. More intensive lipid-lowering therapy was defined as the more potent pharmacological strategy ( PCSK 9 inhibitors, higher intensity statins, or statins), whereas less intensive therapy corresponded to active control group or placebo/usual care of the trial. Metaregression and meta-analyses were conducted using a random-effects model. No significant association was noted between 1-mmol/L reduction in LDL cholesterol and incident DM for more intensive lipid-lowering therapy (risk ratio: 0.95; 95% CI , 0.87-1.04; P=0.30; R2=14%) or for statins or PCSK 9 inhibitors. More intensive lipid-lowering therapy was associated with a higher risk of incident DM compared with less intensive therapy (risk ratio: 1.07; 95% CI , 1.03-1.11; P<0.001; I2=0%). These results were driven by higher risk of incident DM with statins (risk ratio: 1.10; 95% CI , 1.05-1.15; P<0.001; I2=0%), whereas PCSK 9 inhibitors were not associated with incident DM (risk ratio: 1.00; 95% CI , 0.93-1.07; P=0.96; I2=0%; P=0.02 for interaction). Conclusions Among intensive lipid-lowering therapies, there was no independent association between reduction in LDL cholesterol and incident DM . The risk of incident DM was higher with statins, whereas PCSK 9 inhibitors had no association with risk of incident DM .

Meta-Analysis of Efficacy and Safety of Proton Pump Inhibitors with Dual Antiplatelet Therapy for Coronary Artery Disease.

BACKGROUND: There is inconsistency in the literature regarding the clinical effects of proton pump inhibitors (PPI) when added to dual antiplatelet therapy (DAPT) in subjects with coronary artery disease (CAD). We performed meta-analysis stratified by study design to explore these differences. METHODS AND RESULTS: 39 studies [4 randomized controlled trials (RCTs) and 35 observational studies) were selected using MEDLINE, EMBASE and CENTRAL (Inception-January 2018). In 221,204 patients (PPI = 77,731 patients, no PPI =143,473 patients), RCTs restricted analysis showed that PPI did not increase the risk of all-cause mortality (Risk Ratio (RR): 1.35, 95% Confidence Interval (CI), 0.56-3.23, P = 0.50, I2 = 0), cardiovascular mortality (RR: 0.94, 95% CI, 0.25-3.54, P = 0.92, I2 = 56), myocardial infarction (MI) (RR: 0.97, 95% CI, 0.62-1.51, P = 0.88, I2 = 0) or stroke (RR: 1.11, 95% CI, 0.25-5.04, P = 0.89, I2 = 26). However, PPI significantly reduced the risk of gastrointestinal (GI) bleeding (RR: 0.32, 95% CI, 0.20-0.52, P < 0.001, I2 = 0). Conversely, analysis of observational studies showed that PPI significantly increased the risk of all-cause mortality (RR: 1.25, 95% CI, 1.11-1.41, P < 0.001, I2 = 82), cardiovascular mortality (RR: 1.25, 95% CI, 1.03-1.52, P = 0.02, I2 = 71), MI (RR: 1.30, 95% CI, 1.16-1.47, P < 0.001, I2 = 82) and stroke (RR: 1.60, 95% CI, 1.43-1.78, P < 0.001, I2 = 0), without reducing GI bleeding (RR: 0.74, 95% CI, 0.45-1.22, P = 0.24, I2 = 79). CONCLUSION: Meta-analysis of RCTs endorsed the use of PPI with DAPT for reducing GI bleeding without worsening cardiovascular outcomes. These findings oppose the negative observational data regarding effects of PPI with DAPT.

Impella CP Dislodgment, Swap, or Removal: Current Practices.

The Impella CP (ICP) catheter (Abiomed) offers hemodynamic superiority over the intra-aortic balloon pump. However, device-specific issues are occasionally encountered, especially when long-term mechanical circulatory support (MCS) is required. These include ICP dislodgment, ICP mechanical failure, and the need to remove the ICP while maintaining arterial access to either insert a new MCS device or to perform suture-based arteriotomy site closure. We offer a case in which ICP-based MCS involved ICP distal dislodgment, kinking of the ICP catheter, and removal of the device in a coagulopathic and thrombocytopenic patient. The literature regarding potential solutions to these problems is reviewed. Future ICP design is likely to reduce the frequency and complexity of such events and facilitate the management of these scenarios. This is the first report of a novel method to address ICP kinking dislodgment that did not respond to conventional repositioning maneuvers.

Aorto-Right Ventricular Fistula and Paravalvular Leak After Transcatheter Aortic Valve Implantation.

Aorto-right ventricular fistula is a potentially fatal complication following transcatheter aortic valve implantation (TAVI). This paper presents a case of successful percutaneous repair of aorto-right ventricular fistula and paravalvular leak after TAVI by using 3D-printed models for pre-procedural planning, and a review of published aorto-right ventricular fistula cases to date. (Level of Difficulty: Advanced.).

Iliofemoral peripheral orbital atherectomy for optimizing TAVR access: An innovative strategy in the absence of alternative access options.

Suboptimal iliofemoral artery access requiring alternative trans-catheter aortic valve replacement (TAVR) access is still encountered in 10-20% of subjects undergoing TAVR. Attempting suboptimal vascular access may result in excessive vessel injury, bleeding and even death. Reported is an innovative procedure to address suboptimal heavily calcified iliofemoral access by using Diamondback 360 peripheral orbital atherectomy (POA) to ablate heavy endoluminal vascular calcifications followed by balloon angioplasty. This approach enabled us to successfully deploy TAVR in extremely challenging iliofemoral anatomies that would otherwise be rendered prohibitive. The technical aspects of this procedure are delineated accompanied by a descriptive case of such procedure.

Arteriotomy site complication during transcatheter aortic valve replacement: Ipsilateral wire protection and bailout.

Major vascular complications still occur in ~4.2% of transcatheter aortic valve replacement (TAVR) procedures. These complications are a major safety drawback of TAVR when compared to surgical aortic valve replacement (SAVR). Contemporary strategies designed to minimize and effectively treat vascular complications are of immense importance to a successful TAVR program. This review discusses strategies to optimize TAVR access and device choice along with TAVR access complication management. Iliac complications are less frequently encountered and can be managed effectively via the TAVR sheath over the TAVR wire employing ipsilateral proximal iliac balloon occlusion and endovascular repair. The more common arteriotomy site complications and access site closure failure require prophylactic or bail-out common femoral to superficial femoral artery wiring. Suggested is a novel method of ipsilateral arteriotomy site protection that is safe, simple and does not require additional resources. Ipsilateral wiring can also be done prophylactically or as a bailout in case of arteriotomy site complication.

A Bayesian network meta-analysis of PCSK9 inhibitors, statins and ezetimibe with or without statins for cardiovascular outcomes.

Background The comparative effects of statins, ezetimibe with or without statins and proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors remain unassessed. Design Bayesian network meta-analysis was conducted to compare treatment groups. Methods Thirty-nine randomized controlled trials were selected using MEDLINE, EMBASE, and CENTRAL (inception - September 2017). Results In network meta-analysis of 189,116 patients, PCSK9 inhibitors were ranked as the best treatment for prevention of major adverse cardiovascular events (Surface Under Cumulative Ranking Curve (SUCRA), 85%), myocardial infarction (SUCRA, 84%) and stroke (SUCRA, 80%). PCSK9 inhibitors reduced the risk of major adverse cardiovascular events compared with ezetimibe + statin (odds ratio (OR): 0.72; 95% credible interval (CrI), 0.55-0.95; Grading of Recommendation Assessment, Development and Evaluation (GRADE) criteria: moderate), statin (OR: 0.78; 95% CrI: 0.62-0.97; GRADE: moderate) and placebo (OR: 0.63; 95% CrI: 0.49-0.79; GRADE: high). The PCSK9 inhibitors were consistently superior to groups for major adverse cardiovascular event reduction in secondary prevention trials (SUCRA, 95%). Statins had the highest probability of having lowest rates of all-cause mortality (SUCRA, 82%) and cardiovascular mortality (SUCRA, 84%). Compared with placebo, statins reduced the risk of all-cause mortality (OR: 0.88; 95% CrI: 0.83-0.94; GRADE: moderate) and cardiovascular mortality (OR: 0.84; 95% CrI: 0.77-0.90; GRADE: high). For cardiovascular mortality, PCSK9 inhibitors were ranked as the second best treatment (SUCRA, 78%) followed by ezetimibe + statin (SUCRA, 50%). Conclusion PCSK9 inhibitors were ranked as the most effective treatment for reducing major adverse cardiovascular events, myocardial infarction and stroke, without having major safety concerns. Statins were ranked as the most effective therapy for reducing mortality.

Trans-ulnar catheterization and coronary interventions: From technique to outcomes.

The ulnar artery is similar in size to the radial artery, however it is more difficult to palpate and access. For those physicians who mastered trans-ulnar access (TUA) this access site serves as an alternative to trans radial access (TRA) when the radial artery access is rendered suboptimal (by palpation, ultrasound examination or previous procedural records) or when encountering TRA difficulties or failure. The manuscript describes the anatomy, suggested technique, procedural success and complications associated with TUA. Data from single center registries and randomized studies show that TUA has a lower and more variable success rate than TRA, however these 2 approaches carry similar safety profile and complications rates. The authors suggest that interventionalists should consider, learn and master TUA to maintain higher success rate of wrist based interventions while avoiding the potential complications, discomfort and costs of trans-femoral approach.

Simultaneous Two-Vessel Subacute Stent Thrombosis Caused by Clopidogrel Resistance from CYP2C19 Polymorphism.

Clopidogrel resistance from CYP2C19 polymorphism has been associated with stent thrombosis in patients undergoing percutaneous coronary intervention with drug-eluting stents. We present a case of a 76-year-old male who received drug-eluting stents to the right coronary artery and left anterior descending artery for non-ST elevation myocardial infarction and was discharged on dual antiplatelet therapy with aspirin and clopidogrel. He subsequently presented with chest pain from anterior, anteroseptal, and inferior ST segment elevation myocardial infarction. An emergent coronary angiogram revealed acute stent thrombosis with 100% occlusion of RCA and LAD that was successfully treated with thrombus aspiration and angioplasty. Although he was compliant with his dual antiplatelet therapy, he developed stent thrombosis, which was confirmed as clopidogrel resistance from homozygous CYP2C19 polymorphism.

Acute systolic heart failure and uncontrolled hypertension: what is the missing link?

Pheochromocytoma is a rare tumor in adults, with an estimated annual incidence of 0.8 per 100,000 persons. Cardiomyopathy is an uncommon presentation of such a rare disease. Serious cardiovascular complications of these tumors are related to potent effects of secreted catecholamines. The mechanism of pheochromocytoma-related cardiomyopathy is not well understood but it is likely due to the effect of excess catecholamines and their oxidation products which have been found to have a direct toxic effect on the myocardium. We describe below a case of a 70-year old female with uncontrolled hypertension and new onset acute systolic heart failure, who on further evaluation was noted to have pheochromocytoma-related cardiomyopathy. Pheochromocytoma should be strongly considered in the differential diagnosis of non-ischemic cardiomyopathy for a patient with elevated blood pressures relative to severity of cardiac dysfunction.