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International Journal of Molecular... Jan 2024Hypertrophic cardiomyopathy (HCM) is one of the most common genetic cardiovascular diseases, and it shows an autosomal dominant pattern of inheritance. HCM can be... (Review)
Review
Hypertrophic cardiomyopathy (HCM) is one of the most common genetic cardiovascular diseases, and it shows an autosomal dominant pattern of inheritance. HCM can be clinically silent, and sudden unexpected death due to malignant arrhythmias may be the first manifestation. Thus, the HCM diagnosis could be performed at a clinical and judicial autopsy and offer useful findings on morphological features; moreover, it could integrate the knowledge on the genetic aspect of the disease. This review aims to systematically analyze the literature on the main post-mortem investigations and the related findings of HCM to reach a well-characterized and stringent diagnosis; the review was performed using PubMed and Scopus databases. The articles on the post-mortem evaluation of HCM by gross and microscopic evaluation, imaging, and genetic test were selected; a total of 36 studies were included. HCM was described with a wide range of gross findings, and there were cases without morphological alterations. Myocyte hypertrophy, disarray, fibrosis, and small vessel disease were the main histological findings. The post-mortem genetic tests allowed the diagnosis to be reached in cases without morpho-structural abnormalities; clinical and forensic pathologists have a pivotal role in HCM diagnosis; they contribute to a better definition of the disease and also provide data on the genotype-phenotype correlation, which is useful for clinical research.
Topics: Humans; Cardiomyopathy, Hypertrophic; Genetic Testing; Arrhythmias, Cardiac; Autopsy; Fibrosis; Phenotype; Death, Sudden, Cardiac
PubMed: 38279275
DOI: 10.3390/ijms25021275 -
Clinical Cardiology Jan 2024Hypertrophic cardiomyopathy (HCM) is a common contemporary, treatable, genetic disorder that can be compatible with normal longevity. While current medical therapies are... (Review)
Review
Hypertrophic cardiomyopathy (HCM) is a common contemporary, treatable, genetic disorder that can be compatible with normal longevity. While current medical therapies are ubiquitous, they are limited by a lack of solid evidence, are often inadequate, poorly tolerated, and do not alter the natural disease course. As such, there has long been a need for effective, evidence-based, and targeted disease-modifying therapies for HCM. In this review, we redefine HCM as a treatable condition, evaluate current strategies for therapeutic intervention, and discuss novel myosin inhibitors. The majority of patients with HCM have elevated left ventricular outflow tract gradients, which predicts worse symptoms and adverse outcomes. Conventional pharmacological therapies for symptomatic HCM can help improve symptoms but are often inadequate and poorly tolerated. Septal reduction therapies (surgical myectomy and alcohol septal ablation) can safely and effectively reduce refractory symptoms and improve outcomes in patients with obstructive HCM. However, they require expertise that is not universally available and are not without risks. Currently, available therapies do not alter the disease course or the progressive cardiac remodeling that ensues, nor subsequent heart failure and arrhythmias. This has been regarded as an unmet need in the care of HCM patients. Novel targeted pharmacotherapies, namely cardiac myosin inhibitors, have emerged to reverse key pathophysiological changes and alter disease course. Their favorable outcomes led to the early Food and Drug Administration approval of mavacamten, a first-in-class myosin modulator, changing the paradigm for the pharmacological treatment of HCM.
Topics: United States; Humans; Cardiomyopathy, Hypertrophic; Heart; Disease Progression; Heart Failure; Myosins
PubMed: 38269637
DOI: 10.1002/clc.24207 -
Current Problems in Cardiology Mar 2024A systematic review of the literature was conducted to analyze the current evidence on low-flow, low-gradient severe aortic stenosis. This analysis aimed to... (Review)
Review
OBJECTIVES
A systematic review of the literature was conducted to analyze the current evidence on low-flow, low-gradient severe aortic stenosis. This analysis aimed to differentiate between subgroups of patients with reduced and preserved left ventricular ejection fraction (LVEF).
METHODS
After conducting a systematic literature review, 35 observational studies were included. Out of these, 28 were prospective and 7 retrospective. The studies that included a mortality risk stratification of low-flow, low-gradient aortic stenosis (LF- LG AS) with both preserved and reduced LVEF were reviewed.
RESULTS
The importance of considering multiple clinical and echocardiographic variables in diagnostic evaluation and therapeutic decision-making was highlighted.
CONCLUSIONS
LF- LG AS, in any of its subgroups, is a common and challenging valve lesion. A careful assessment of severity and, in specific scenarios, a thorough reclassification is important. More high-quality studies are required to more precisely define the classification and prognosis of this entity.
Topics: Humans; Stroke Volume; Ventricular Function, Left; Retrospective Studies; Prospective Studies; Aortic Valve Stenosis; Severity of Illness Index; Aortic Valve; Heart Valve Prosthesis Implantation
PubMed: 38232925
DOI: 10.1016/j.cpcardiol.2024.102392 -
Open Heart Jan 2024A quarter of patients with severe aortic stenosis (AS) were asymptomatic, and only a third of them survived at the end of 4 years. Only a select subset of these patients... (Meta-Analysis)
Meta-Analysis
Systematic review and meta-analysis of early aortic valve replacement versus conservative therapy in patients with asymptomatic aortic valve stenosis with preserved left ventricle systolic function.
BACKGROUND
A quarter of patients with severe aortic stenosis (AS) were asymptomatic, and only a third of them survived at the end of 4 years. Only a select subset of these patients was recommended for aortic valve replacement (AVR) by the current American College of Cardiology/American Heart Association guidelines. We intended to study the effect of early AVR (eAVR) in this subset of asymptomatic patients with preserved left ventricle function.
METHODS AND RESULTS
We searched PubMed and Embase for randomised and observational studies comparing the effect of eAVR versus conservative therapy in patients with severe, asymptomatic AS and normal left ventricular function. The primary outcome was all-cause mortality. The secondary outcomes were composite major adverse cardiac events (MACE) (study defined), myocardial infarction (MI), stroke, cardiac death, sudden death, the development of symptoms, heart failure hospitalisations and major bleeding. We used GRADEPro to assess the certainty of the evidence. In the randomised controlled trial (RCT) only analysis, we found no significant difference in all-cause mortality between the early aortic intervention group versus the conservative arm (CA) (incidence rate ratio, IRR (CI): 0.5 (0.2 to 1.1), I=31%, p=0.09). However, in the overall cohort, we found mortality benefit for eAVR over CA (IRR (CI): 0.4 (0.3 to 0.7), I=84%, p<0.01). There were significantly lower MACE, cardiac death, sudden death, development of symptoms and heart failure hospitalisations in the eAVR group. We noticed no difference in MI, stroke and major bleeding.
CONCLUSION
We conclude that there is no reduction in all-cause mortality in the eAVR arm in patients with asymptomatic AS with preserved ejection fraction. However, eAVR reduces heart failure related hospitalisations and death or heart failure hospitalisations.
PROSPERO REGISTRATION NUMBER
CRD42022306132.
Topics: Humans; Aortic Valve; Aortic Valve Stenosis; Conservative Treatment; Death, Sudden, Cardiac; Heart Failure; Hemorrhage; Myocardial Infarction; Stroke; United States; Ventricular Function, Left; Heart Valve Prosthesis Implantation; Transcatheter Aortic Valve Replacement
PubMed: 38191233
DOI: 10.1136/openhrt-2023-002511 -
International Journal of Cardiology Mar 2024Carotid Artery Stenosis (CAS) is common in elderly patients undergoing Transcatheter Aortic Valve Replacement (TAVR). However, the impact of CAS on the outcomes of TAVR... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Carotid Artery Stenosis (CAS) is common in elderly patients undergoing Transcatheter Aortic Valve Replacement (TAVR). However, the impact of CAS on the outcomes of TAVR is unclear.
PURPOSE
This systematic review and meta-analysis aimed to compare the clinical and periprocedural outcomes in patients with and without CAS undergoing TAVR.
METHODS
PubMed, Embase, and Cochrane databases were searched until February 2023. We included studies that performed a direct comparison of outcomes of TAVR in CAS versus non-CAS patients. Data was extracted from published reports and the ROBINS-I tool was utilized for quality assessment. The R studio software (version 4.2.2) was adopted for statistical analysis.
RESULTS
Five observational studies and 111.915 patients were included. The mean age was 80.7 ± 8.2 years and 46.3% were female. The risk of stroke or transient ischemic attack was elevated in the group of patients with CAS (OR 1.44; 95% CI 1.07-1.95; p = 0.016). In contrast, myocardial infarction (OR 1.24; 95% CI 1.05-1.47; p = 0.074) and all-cause mortality (OR 0.99; 95% CI 0.73-1.35; p = 0.95) were not significantly different between CAS and non-CAS groups. Acute kidney injury and new pacemaker implantation did not differ between patients with and without CAS.
CONCLUSIONS
Our findings suggest that CAS is significantly associated with cerebrovascular events in patients undergoing TAVR, without significantly impacting all-cause mortality. Further prospective studies are needed for a more granular assessment of additional determinants of this association, such as unilateral vs. bilateral involvement and whether there is a threshold of CAS severity for increased risk.
Topics: Humans; Female; Aged; Aged, 80 and over; Male; Transcatheter Aortic Valve Replacement; Carotid Stenosis; Aortic Valve Stenosis; Risk Factors; Treatment Outcome; Aortic Valve
PubMed: 38141726
DOI: 10.1016/j.ijcard.2023.131670 -
Current Problems in Cardiology Mar 2024Transcatheter aortic valve implantation (TAVI) is a common practice for severe aortic stenosis, but the choice between general (GA) and local anesthesia (LA) remains... (Meta-Analysis)
Meta-Analysis Review
Local versus General Anaesthesia for Transcatheter Aortic Valve Implantation (TAVI): A Systematic Review, Meta-Analysis, and Trial Sequential Analysis of Randomised and Propensity-Score Matched Studies.
Transcatheter aortic valve implantation (TAVI) is a common practice for severe aortic stenosis, but the choice between general (GA) and local anesthesia (LA) remains uncertain. We conducted a comprehensive literature review until April 2023, comparing the safety and efficacy of LA versus GA in TAVI procedures. Our findings indicate significant advantages of LA, including lower 30-day mortality rates (RR: 0.69; 95% CI [0.58, 0.82]; p < 0.001), shorter in-hospital stays (mean difference: -0.91 days; 95% CI [-1.63, -0.20]; p = 0.01), reduced bleeding/transfusion incidents (RR: 0.64; 95% CI [0.48, 0.85]; p < 0.01), and fewer respiratory complications (RR: 0.56; 95% CI [0.42, 0.76], p<0.01). Other operative outcomes were comparable. Our findings reinforce prior evidence, presenting a compelling case for LA's safety and efficacy. While patient preferences and clinical nuances must be considered, our study propels the discourse towards a more informed anaesthesia approach for TAVI procedures.
Topics: Humans; Transcatheter Aortic Valve Replacement; Aortic Valve Stenosis; Treatment Outcome; Anesthesia, General; Anesthesia, Local; Aortic Valve; Heart Valve Prosthesis Implantation; Risk Factors
PubMed: 38128636
DOI: 10.1016/j.cpcardiol.2023.102360 -
Cureus Nov 2023Aortic valve replacement (AVR) successfully treats aortic valve stenosis and aortic regurgitation from aging or bicuspid aortic valves. The procedure intends to restore... (Review)
Review
Aortic valve replacement (AVR) successfully treats aortic valve stenosis and aortic regurgitation from aging or bicuspid aortic valves. The procedure intends to restore the obstructed left ventricular outflow tract (LVOT). AVR can be performed surgically (surgical aortic valve replacement (SAVR); open heart) or via transcatheter (transcatheter aortic valve replacement (TAVR)), typically done through a femoral approach as a minimally invasive procedure, allowing for quicker recovery and reduced hospital stays. AVR has many complications, including life-threatening ones, such as infective endocarditis (IE), retarding the recovery process and increasing mortality following surgery. IE is an uncommon and deadly condition that involves multiple organ systems and is caused by bacteremia stemming from a microorganism that enters the bloodstream. Many manifestations are involved in the development of IE, such as fevers, flu-like symptoms, splinter hemorrhages, Osler nodes, abscesses, and vegetations found on the valves at the leaflets. Vegetations and abscesses tend to create further complications, such as stroke and acute kidney injury, as emboli block blood flow, leading to ischemia and damage. This paper aims to evaluate the difference in SAVR- and TAVR-associated IE, as the goal is to elucidate a danger that diminishes the positive effects of either procedure despite its rarity. Studies have been inconclusive in determining whether or not there is a trend, let alone a difference in incident rates. Both procedures share similar risk factors, but SAVR-associated IE is usually caused by and studies indicate possibly in TAVR-associated IE. Incident rates of IE are much higher than they should be, whether or not they differ between procedures, and future research needs to consider the pathways and risk factors that can be used to reduce the occurrence of AVR-associated IE.
PubMed: 38116334
DOI: 10.7759/cureus.49048 -
Heart Failure Reviews Mar 2024Hypertrophic cardiomyopathy (HCM) is the most common heritable myocardial disorder worldwide. Current pharmacological treatment options are limited. Mavacamten, a... (Meta-Analysis)
Meta-Analysis Review
Hypertrophic cardiomyopathy (HCM) is the most common heritable myocardial disorder worldwide. Current pharmacological treatment options are limited. Mavacamten, a first-in-class cardiac myosin inhibitor, targets the main underlying pathology of HCM. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of Mavacamten in patients with HCM. PRISMA flow chart was utilized using PubMed, SCOPUS, and Cochrane databases for all up-to-date studies using pre-defined keywords. Pre-specified efficacy outcomes comprised several parameters, including an improvement in peak oxygen consumption (pVO2) and ≥ 1 NYHA class, the need for septal reduction therapy (SRT), change from baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ), changes in biochemical markers and LVEF, along with peak left ventricular outflow tract gradient at rest and after Valsalva maneuver. Safety outcomes included morbidity and serious adverse events. This systematic review included five studies, four RCTs and one non-randomized control trial comprised a total of 524 (Mavacamten [273, 54.3%] vs placebo [230, 45.7%] adult (≥ 18 years) patients with a mean age of 56 years. The study. comprised patients with Caucasian and Chinese ethnicity and patients with obstructive (oHCM) and non-obstructive (nHCM) HCM. Most baseline characteristics were similar between the treatment and placebo groups. Mavacamten showed a statistically significant increase in the frequency of the primary composite endpoint (RR = 1.92, 95% CI [1.28, 2.88]), ≥ 1 NYHA class improvement (RR = 2.10, 95% CI [1.66, 2.67]), a significant decrease in LVEF, peak left ventricular outflow tract gradient at rest and after Valsalva maneuver. Mavacamten also showed a significant reduction in SRT rates (RR = 0.29, 95% CI [0.21, 0.40], p < 0.00001), KCCQ clinical summary scores (MD = 8.08, 95% CI [4.80, 11.37], P < 0.00001) troponin levels and N-terminal pro-B-type natriuretic peptide levels. However, there was no statistically significant difference between Mavacamten and placebo regarding the change from baseline peak oxygen consumption. Mavacamten use resulted in a small increase in adverse events but no statistically significant increment in serious adverse events. Our study showed that Mavacamten is a safe and effective treatment option for Caucasian and Chinese patients with HCM on the short-term. Further research is needed to explore the long-term safety and efficacy of Mavacamten with HCM. In addition, adequately powered studies including patients with nHCM is needed to ascertain befits of Mavacamten in those patients.
Topics: Adult; Humans; Middle Aged; Cardiomyopathy, Hypertrophic; Heart; Benzylamines; Myocardium; Uracil
PubMed: 38112937
DOI: 10.1007/s10741-023-10375-6 -
The American Journal of Cardiology Mar 2024Acute hemodynamic compromise after transcatheter aortic valve replacement (TAVR) because of dynamic left ventricle (LV) obstruction (LVO), also known as suicide LV, is...
Acute hemodynamic compromise after transcatheter aortic valve replacement (TAVR) because of dynamic left ventricle (LV) obstruction (LVO), also known as suicide LV, is an infrequent but severe complication of TAVR that is poorly defined in previous studies. Understanding this complication is essential for its prompt diagnosis and optimal treatment. We conducted a systematic literature review using PubMed, Embase, Web of Science, and Medline databases for studies describing acute hemodynamic compromise after TAVR because of dynamic LVO or suicide LV. Each study was reviewed by 2 authors individually for eligibility, and a third author resolved disagreements. From a total of 506 studies, 25 publications were considered for the final analysis. The majority of patients with this condition were women demonstrating a hypertrophic septum, a small ventricle, and hyperdynamic contractility on pre-TAVR echocardiographic assessment. An intraventricular gradient before TAVR was found in half of the cases. Acute hemodynamic compromise after TAVR because of dynamic LVO manifested mainly as significant hypotension and occurred most often immediately after valve deployment. The LV outflow tract was the most common site of obstruction. Advanced therapies were required in nearly 65% of the cases. In conclusion, acute hemodynamic compromise after TAVR because of dynamic LVO occurred almost invariably in women. Echocardiography before TAVR may offer essential information to anticipate this complication. LV outflow tract obstruction appears to carry the highest risk of developing this phenomenon. Advanced therapies should be promptly considered as a bailout strategy in patients with hemodynamic collapse refractory to medical therapy.
Topics: Humans; Male; Female; Transcatheter Aortic Valve Replacement; Aortic Valve Stenosis; Heart Ventricles; Treatment Outcome; Hemodynamics; Aortic Valve; Ventricular Function, Left
PubMed: 38103763
DOI: 10.1016/j.amjcard.2023.12.005 -
Clinical Medicine (London, England) Nov 2023Recent randomised trials have shown that clinical outcomes with transcatheter aortic valve implantation (TAVI) are non-inferior to surgical aortic valve replacement... (Meta-Analysis)
Meta-Analysis Review
Recent randomised trials have shown that clinical outcomes with transcatheter aortic valve implantation (TAVI) are non-inferior to surgical aortic valve replacement (SAVR) in patients with symptomatic aortic stenosis at intermediate to low risk. Health-related quality of life (HrQoL) outcomes in these patient groups remain uncertain. A systematic search of the literature was conducted that included nine trials and 11,295 patients. Kansas City Cardiomyopathy Questionnaire (KCCQ), a heart-failure-specific measure and EuroQol-5D (EQ-5D) (a generic health status tool) changes were the primary outcomes. New York Heart Association (NYHA) classification was the secondary outcome. Improvement in KCCQ scores was greater with TAVI (mean difference (MD)=13.56, 95% confidence interval (CI) 11.67-15.46, p<0.001) at 1 month, as was the improvement in EQ-5D (MD=0.07, 95% CI 0.05-0.08, p<0.001). There was no difference in KCCQ (MD=1.05, 95% CI -0.11 to 2.21, p=0.08) or EQ-5D (MD=-0.01, 95% CI -0.03 to 0.01), p=0.37) at 12 months. NYHA functional class 3/4 was lower in patients undergoing TAVI at 1 month (MD=0.51, 95% CI 0.34-0.78, p=0.002), but there was no difference at 12 months (MD=1.10; 95% CI 0.87-1.38, p=0.43). Overall, TAVI offers early benefit in HRQoL outcomes compared with SAVR, but they are equivalent at 12 months.
Topics: Humans; Transcatheter Aortic Valve Replacement; Quality of Life; Aortic Valve Stenosis; Aortic Valve; Risk; Treatment Outcome; Risk Factors
PubMed: 38065591
DOI: 10.7861/clinmed.2023-0258