Cardiomyopathy in First-Degree Relatives of Patients Presenting With Acute Myocarditis: Prevalence and Prognostic Significance.

BACKGROUND: Acute myocarditis has been genetically linked to dilated cardiomyopathy (DCM), but the clinical significance remains uncertain. We investigated the prevalence and long-term prognosis of DCM and heart failure (HF) among unselected patients hospitalized with acute myocarditis and their first-degree relatives compared with an age- and sex-matched cohort. METHODS: This was an observational study utilizing the Danish nationwide registries, where all patients with a first-time myocarditis diagnosis from 1995 to 2018 were identified and matched (on birth year and sex) with 10 controls from the general population. RESULTS: Totally 3176 patients with acute myocarditis and 31 760 controls were included (median age, 49.8 [Q1-Q3, 32.5-70.2] years; 35.6% female). At baseline, patients with myocarditis had a higher prevalence of DCM (7 [0.2%] versus 8 [0.0%]) and HF (336 [10.6%] versus 695 [2.2%]) than controls; P<0.0001 for both. Patients with myocarditis more often had siblings with DCM (12 [0.4%] versus 17 [0.05%]) or HF (36 [1.1%] versus 89 [0.3%]); P<0.0001, odds ratios 7.09 (3.38-14.85) and 2.92 (1.25-6.80), respectively, whereas parental DCM and HF did not differ among patients with myocarditis and controls. Patients with myocarditis had greater 20-year incidence of DCM, HF, and all-cause mortality (0.5% [0.3%-0.9%], 15% [13%-17%], and 47% [44%-50%]) compared with controls (0.06% [0.03%-0.11%], 6.8% [6.4%-7.3%], and 34% [33%-35%]; P<0.0001). Having a first-degree relative with DCM or HF was associated with increased long-term mortality among the patients with myocarditis (hazard ratio, 1.40 [1.11-1.77]) but not among the controls (hazard ratio, 0.90 [0.81-1.01]; Pdifference=0.0008). CONCLUSIONS: Acute myocarditis aggregates with DCM within families, where it carries a worsened prognosis. A differential association between parents and siblings (with sibling preponderance) could suggest that additional environmental factors are important for myocarditis development even in predisposed individuals.

Clinical characteristics, treatment, trajectories and outcome of patients with dilated cardiomyopathy in a national heart failure registry.

BACKGROUND: Available data on the clinical characteristics and prognosis of patients with heart failure (HF) due to dilated cardiomyopathy (DCM) derive mainly from tertiary care centres for cardiomyopathies or from drug trial sub-studies, which may entail a referral bias. METHODS: From 2008 to 2021, we enrolled in a nationwide HF Registry 1886 DCM patients and 3899 with ischemic heart disease (IHD). RESULTS: Patients with DCM were younger, more often female, had more commonly recent onset HF, left bundle branch block, and showed higher LV end-diastolic volume and lower LVEF than IHD. With respect to IHD, DCM patients received more often mineralocorticoid receptor antagonists, renin angiotensin system inhibitors and betablockers, the latter more commonly at doses ≥50% of target, and triple guideline-directed medical therapy (GDMT) (adjusted OR 1.411, 95% CI 1.247-1.595, p < .0001). During one-year follow-up, 819 patients (14.2%) died or were hospitalized for HF [187 (9.9%) DCM, 632 (16.2%) IHD]; DCM was associated with lower risk of the combined end-point (adjusted HR 0.745, 95% CI 0.625- 0.888, p = .0011). Among the 1954 patients with 1-year echocardiograms available, 1483 had LVEF≤40% at baseline; of these,166 (30.6%) DCM and 165 (17.5%) IHD improved their LVEF to >40% (p < .0001). DCM aetiology was associated with higher likelihood of LVEF improvement (adjusted OR 1.722, 95% CI 1.328 -2.233, p < .0001). CONCLUSIONS: DCM patients have a different clinical profile, greater uptake of GDMT and better outcomes than IHD subjects. A comprehensive management approach is needed to further address the risk of unfavorable outcomes in DCM.

[Seroprevalence of Chagas disease at the Instituto Nacional de Cardiología Ignacio Chávez from 2004 to 2010]. / Prevalencia de cardiomiopatía dilatada en pacientes seropositivos a Trypanosoma cruzi en el Instituto Nacional Cardiología Ignacio Chávez de 2004 al 2010.

Background: Different pathogens can cause dilated cardiomyopathy, one of them is Trypanosoma cruzi protozoan. T.cruzi-chronic infection causes chronic Chagasic cardiomyopathy and affects the sinus node and the conduction systembelow the bundle of His; besides, it shows excellent arrhythmogenic potential because of ventricular arrhythmias. Knowingthe clinical characteristics and performing serological tests to diagnose chronic Chagasic cardiomyopathy is essential. The serological diagnosis for searching the antibodies is based on the phase, which can be a predictor for the development of dilated cardiomyopathy. Objectives: In this work, the objective was to describe the frequency of dilated cardiomyopathy in patients with T. cruzi positive serology. Method: A total of 961 patients who were medically and clinically diagnosed with dilated cardiomyopathy were studied. Of these, 128 were diagnosed with chronic Chagasic cardiomyopathy and had positive serology for T. cruzi with two serological tests. Results: The clinical findings were obtained from the results of the electrocardiograms and were taken from the patient's clinical histories. Conclusion: In conclusion, complete blockage of the right branch of the bundle of His (44.2%) is one of the primary conduction disorders in the patients studied. Regarding seroprevalence, 14% of patients diagnosed with dilated cardiomyopathy had anti-T. cruzi antibodies.

Antecedentes: La cardiomiopatía dilatada puede ser causada por diferentes patógenos y uno de ellos es el protozoario Trypanosoma cruzi. La infección crónica causa la cardiomiopatía chagásica crónica, que afecta el nódulo sinusal y el sistema de conducción a nivel del haz de His; además, muestra gran potencial arritmogénico, ya que frecuentemente se presentan arritmias ventriculares. Para diagnosticar la cardiomiopatía chagásica crónica es indispensable conocer las características clínicas y realizar los ensayos serológicos. El diagnóstico serológico para la búsqueda de anticuerpos se basa en la fase de la enfermedad en la que se encuentre el individuo, los cuales pueden ser un predictor para el desarrollo de la cardiomiopatía dilatada. Objetivo: El objetivo de nuestro trabajo fue describir la frecuencia de cardiomiopatía dilatada en pacientes con serología positiva a T. cruzi en el Instituto Nacional de Cardiología Ignacio Chávez. Método: Se estudiaron 961 pacientes que fueron diagnosticados médica y clínicamente con cardiomiopatía dilatada y, de estos, 128 fueron diagnosticados con cardiomiopatía chagásica crónica, los cuales presentaban serología positiva a T. cruzi con dos pruebas serológicas. Resultados: Los hallazgos clínicos se obtuvieron de los resultados de los electrocardiogramas y fueron tomados de las historias clínicas de los pacientes. Conclusiones: En conclusión, el bloqueo completo de la rama derecha del haz de His (44.2%) es una de las principales alteraciones de la conducción en los pacientes estudiados. Con respecto a la seroprevalencia, el 14% de los pacientes con diagnóstico de cardiomiopatía dilatada tuvieron anticuerpos anti-T. cruzi.

Characterization of Non-Ischemic Dilated Cardiomyopathy in a Native Tanzanian Cohort: MOYO Study.

Background: Non-ischemic dilated cardiomyopathy (NIDCM) is a common cause of heart failure with progressive tendency. The disease occurs in one in every 2,500 individuals in the developed world, with high morbidity and mortality. However, detailed data on the role of NIDCM in heart failure in Tanzania is lacking. Aim: To characterize NIDCM in a Tanzanian cohort with respect to demographics, clinical profile, imaging findings and management. Methods: Characterization of non-ischemic dilated cardioMyOpathY in a native Tanzanian cOhort (MOYO) is a prospective cohort study of NIDCM patients seen at the Jakaya Kikwete Cardiac Institute. Patients aged ≥18 years with a clinical diagnosis of heart failure, an ejection fraction of ≤45% on echocardiography and no evidence of ischemia were enrolled. Clinical data, echocardiography, electrocardiography (ECG), coronary angiography and stress ECG information were collected from February 2020 to March 2022. Results: Of 402 patients, n = 220 (54.7%) were males with a median (IQR) age of 55.0 (41.0, 66.0) years. Causes of NIDCM were presumably hypertensive n = 218 (54.2%), idiopathic n = 116 (28.9%), PPCM n = 45 (11.2%), alcoholic n = 10 (2.5%) and other causes n = 13 (3.2%). The most common presenting symptoms were dyspnea n = 342 (85.1%), with the majority of patients presenting with New York Heart Association (NYHA) Class III n = 195 (48.5%). The mean (SD) left ventricular ejection fraction (LVEF) was 29.4% (±7.7), and severe systolic dysfunction (LVEF <30%) was common n = 208 (51.7%). Compared with other forms of DCM, idiopathic DCM patients were significantly younger, had more advanced NYHA class (p < 0.001) and presented more often with left bundle branch block on ECG (p = 0.0042). There was suboptimal use of novel guidelines recommended medications ARNI n = 10 (2.5%) and SGLT2 2-inhibitors n = 2 (0.5%). Conclusions: In our Tanzanian cohort, the majority of patients with NIDCM have an identified underlying cause, and they present at late stages of the disease. Patients with idiopathic DCM are younger with more severe disease compared to other forms of NIDCM.

Clinical Trajectories and Long-Term Outcomes of Alcoholic Versus Other Forms of Dilated Cardiomyopathy.

BACKGROUND: Alcoholic cardiomyopathy (ACM) is a form of dilated cardiomyopathy (DCM) occurring secondary to long-standing heavy alcohol use and is associated with poor outcomes, but the cause-specific risks are insufficiently understood. METHOD: Between 1997 and 2018, we identified all patients with a first diagnosis of ACM or DCM. The cumulative incidence of different causes of hospitalisation and mortality in the two groups was calculated using the Fine-Gray and Kaplan-Meier methods. RESULTS: A Total of 1,237 patients with ACM (mean age 56.3±10.1 years, 89% men) and 17,211 individuals with DCM (mean age 63.6±13.8 years, 71% men) were identified. Diabetes (10% vs 15%), hypertension (22% vs 31%), and stroke (8% vs 10%) were less common in ACM than DCM, whereas obstructive lung disease (15% vs 12%) and liver disease (17% vs 2%) were more prevalent (p<0.05). Cumulative 5-year mortality was 49% in ACM vs 33% in DCM, p<0.0001, multivariable adjusted hazards ratio 2.11 (95% confidence interval 1.97-2.26). The distribution of causes of death was similar in ACM and DCM, with the predominance of cardiovascular causes in both groups (42% in ACM vs 44% in DCM). 5-year cumulative incidence of heart failure hospitalisations (48% vs 54%) and any somatic cause (59% vs 65%) were also similar in ACM vs DCM. At 1 year, the use of beta blockers (55% vs 80%) and implantable cardioverter defibrillators (3% vs 14%) were significantly less often used in ACM vs DCM. CONCLUSIONS: Patients with ACM had similar cardiovascular risks and hospitalisation patterns as other forms of DCM, but lower use of guideline-directed cardiovascular therapies and greater mortality.

Inherited Arrhythmias in the Pediatric Population: An Updated Overview.

Pediatric cardiomyopathies (CMs) and electrical diseases constitute a heterogeneous spectrum of disorders distinguished by structural and electrical abnormalities in the heart muscle, attributed to a genetic variant. They rank among the main causes of morbidity and mortality in the pediatric population, with an annual incidence of 1.1-1.5 per 100,000 in children under the age of 18. The most common conditions are dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM). Despite great enthusiasm for research in this field, studies in this population are still limited, and the management and treatment often follow adult recommendations, which have significantly more data on treatment benefits. Although adult and pediatric cardiac diseases share similar morphological and clinical manifestations, their outcomes significantly differ. This review summarizes the latest evidence on genetics, clinical characteristics, management, and updated outcomes of primary pediatric CMs and electrical diseases, including DCM, HCM, arrhythmogenic right ventricular cardiomyopathy (ARVC), Brugada syndrome (BrS), catecholaminergic polymorphic ventricular tachycardia (CPVT), long QT syndrome (LQTS), and short QT syndrome (SQTS).

Phenotype, outcomes and natural history of early-stage non-ischaemic cardiomyopathy.

AIMS: To characterize the phenotype, clinical outcomes and rate of disease progression in patients with early-stage non-ischaemic cardiomyopathy (early-NICM). METHODS AND RESULTS: We conducted a prospective observational cohort study of patients with early-NICM assessed by late gadolinium enhancement cardiovascular magnetic resonance (CMR). Cases were classified into the following subgroups: isolated left ventricular dilatation (early-NICM H-/D+), non-dilated left ventricular cardiomyopathy (early-NICM H+/D-), or early dilated cardiomyopathy (early-NICM H+/D+). Clinical follow-up for major adverse cardiovascular events (MACE) included non-fatal life-threatening arrhythmia, unplanned cardiovascular hospitalization or cardiovascular death. A subset of patients (n = 119) underwent a second CMR to assess changes in cardiac structure and function. Of 254 patients with early-NICM (median age 46 years [interquartile range 36-58], 94 [37%] women, median left ventricular ejection fraction [LVEF] 55% [52-59]), myocardial fibrosis was present in 65 (26%). There was no difference in the prevalence of fibrosis between subgroups (p = 0.90), however fibrosis mass was lowest in early-NICM H-/D+, higher in early-NICM H+/D- and highest in early-NICM H+/D+ (p = 0.03). Over a median follow-up of 7.9 (5.5-10.0) years, 28 patients (11%) experienced MACE. Non-sustained ventricular tachycardia (hazard ratio [HR] 5.1, 95% confidence interval [CI] 2.36-11.00, p < 0.001), myocardial fibrosis (HR 3.77, 95% CI 1.73-8.20, p < 0.001) and diabetes mellitus (HR 5.12, 95% CI 1.73-15.18, p = 0.003) were associated with MACE in a multivariable model. Only 8% of patients progressed from early-NICM to dilated cardiomyopathy with LVEF <50% over a median of 16 (11-34) months. CONCLUSION: Early-NICM is not benign. Fibrosis develops early in the phenotypic course. In-depth characterization enhances risk stratification and might aid clinical management.

Rare Variant Genetics and Dilated Cardiomyopathy Severity: The DCM Precision Medicine Study.

BACKGROUND: Dilated cardiomyopathy (DCM) can lead to advanced disease, defined herein as necessitating a durable left ventricular assist device or a heart transplant (LVAD/HT). DCM is known to have a genetic basis, but the association of rare variant genetics with advanced DCM has not been studied. METHODS: We analyzed clinical and genetic sequence data from patients enrolled between 2016 and 2021 in the US multisite DCM Precision Medicine Study, which was a geographically diverse, multiracial, multiethnic cohort. Clinical evaluation included standardized patient interview and medical record query forms. DCM severity was classified into 3 groups: patients with advanced disease with LVAD/HT; patients with an implantable cardioverter defibrillator (ICD) only; or patients with no ICD or LVAD/HT. Rare variants in 36 DCM genes were classified as pathogenic or likely pathogenic or variants of uncertain significance. Confounding factors we considered included demographic characteristics, lifestyle factors, access to care, DCM duration, and comorbidities. Crude and adjusted associations between DCM severity and rare variant genetic findings were assessed using multinomial models with generalized logit link. RESULTS: Patients' mean (SD) age was 51.9 (13.6) years; 42% were of African ancestry, 56% were of European ancestry, and 44% were female. Of 1198 patients, 347 had LVAD/HT, 511 had an ICD, and 340 had no LVAD/HT or ICD. The percentage of patients with pathogenic or likely pathogenic variants was 26.2%, 15.9%, and 15.0% for those with LVAD/HT, ICD only, or neither, respectively. After controlling for sociodemographic characteristics and comorbidities, patients with DCM with LVAD/HT were more likely than those without LVAD/HT or ICD to have DCM-related pathogenic or likely pathogenic rare variants (odds ratio, 2.3 [95% CI, 1.5-3.6]). The association did not differ by ancestry. Rare variant genetic findings were similar between patients with DCM with an ICD and those without LVAD/HT or ICD. CONCLUSIONS: Advanced DCM was associated with higher odds of rare variants in DCM genes adjudicated as pathogenic or likely pathogenic, compared with individuals with less severe DCM. This finding may help assess the risk of outcomes in management of patients with DCM and their at-risk family members. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03037632.

Clinical characteristics of heart failure with reduced ejection fraction patients with rare pathogenic variants in dilated cardiomyopathy-associated genes: A subgroup analysis of the PARADIGM-HF trial.

AIMS: To evaluate the prevalence of pathogenic variants in genes associated with dilated cardiomyopathy (DCM) in a clinical trial population with heart failure and reduced ejection fraction (HFrEF) and describe the baseline characteristics by variant carrier status. METHODS AND RESULTS: This was a post hoc analysis of the Phase 3 PARADIGM-HF trial. Forty-four genes, divided into three tiers, based on definitive, moderate or limited evidence of association with DCM, were assessed for rare predicted loss-of-function (pLoF) variants, which were prioritized using ClinVar annotations, measures of gene transcriptional output and evolutionary constraint, and pLoF confidence predictions. Prevalence was reported for pLoF variant carriers based on DCM-associated gene tiers. Clinical features were compared between carriers and non-carriers. Of the 1412 HFrEF participants with whole-exome sequence data, 68 (4.8%) had at least one pLoF variant in the 8 tier-1 genes (definitive/strong association with DCM), with Titin being most commonly affected. The prevalence increased to 7.5% when considering all 44 genes. Among patients with idiopathic aetiology, 10.0% (23/229) had tier-1 variants only and 12.6% (29/229) had tier-1, -2 or -3 variants. Compared to non-carriers, tier-1 carriers were younger (4 years; adjusted p-value [padj ] = 4 × 10-3 ), leaner (27.8 kg/m2 vs. 29.4 kg/m2 ; padj = 3.2 × 10-3 ), had lower ejection fraction (27.3% vs. 29.8%; padj = 5.8 × 10-3 ), and less likely to have ischaemic aetiology (37.3% vs. 67.4%; padj = 4 × 10-4 ). CONCLUSION: Deleterious pLoF variants in genes with definitive/strong association with DCM were identified in ∼5% of HFrEF patients from a PARADIGM-HF trial subset, who were younger, had lower ejection fraction and were less likely to have had an ischaemic aetiology.

Prevalence and clinical correlates of ascending aortic dilatation in patients with noncompaction cardiomyopathy.

Ascending aortic (AoAsc) dilatation can lead to acute aortic syndromes and has been described in various familial cardiac diseases. Its prevalence and clinical significance in patients with noncompaction cardiomyopathy (NCCM) are however unknown. Establishing the prevalence can facilitate recommendations on routine screening in NCCM. In this cross-sectional cohort study based on the Rijnmond Heart Failure/Cardiomyopathy Registry, the patient were enrolment between 2014 and 2021. All NCCM patients (n = 109) were age and sex matched with 109 dilated cardiomyopathy (DCM) patients as controls. The aortic diameters were measured through the parasternal long-axis transthoracic echocardiographic view at the sinuses of valsalva (SoV-Ao), sinotubular junction (STJ) and ascending aorta (AscAo). Dilatation was defined using published criteria adjusted for body surface area (BSA), sex, and age. Median age of age-sex matched NCCM and DCM patients was 45[31-56] vs. 45 [31-55] years with 53% males in both groups. NCCM patients had more familial hereditary patterns and genetic variants (55% vs. 24%, p < 0.001). DCM patients had more heart failure and left ventricular dysfunction (ejection fraction 34 ± 11 vs. 41 ± 12, p = 0.001). Ascending aortic dilatation was present in 8(7%) patients with NCCM and 5(5%) patients with DCM (p = 0.46). All dilatations were classified as mild. In conclusion, in this cross-sectional cohort study the prevalence of ascending aortic dilatation in NCCM patients was 7%, which were only mild dilatations and not significantly different from an age-sex matched cohort of DCM patients. Routine aortic dilatation screening therefore does not seem warranted in patients with NCCM.

Prevalence and Clinical Consequences of Multiple Pathogenic Variants in Dilated Cardiomyopathy.

BACKGROUND: Dilated cardiomyopathy (DCM) was considered a monogenetic disease that can be caused by over 60 genes. Evidence suggests that the combination of multiple pathogenic variants leads to greater disease severity and earlier onset. So far, not much is known about the prevalence and disease course of multiple pathogenic variants in patients with DCM. To gain insight into these knowledge gaps, we (1) systematically collected clinical information from a well-characterized DCM cohort and (2) created a mouse model. METHODS: Complete cardiac phenotyping and genotyping was performed in 685 patients with consecutive DCM. Compound heterozygous digenic (LMNA [lamin]/titin deletion A-band) with monogenic (LMNA/wild-type) and wild-type/wild-type mice were created and phenotypically followed over time. RESULTS: One hundred thirty-one likely pathogenic/pathogenic (LP/P) variants in robust DCM-associated genes were found in 685 patients with DCM (19.1%) genotyped for the robust genes. Three of the 131 patients had a second LP/P variant (2.3%). These 3 patients had a comparable disease onset, disease severity, and clinical course to patients with DCM with one LP/P. The LMNA/Titin deletion A-band mice had no functional differences compared with the LMNA/wild-type mice after 40 weeks of follow-up, although RNA-sequencing suggests increased cardiac stress and sarcomere insufficiency in the LMNA/Titin deletion A-band mice. CONCLUSIONS: In this study population, 2.3% of patients with DCM with one LP/P also have a second LP/P in a different gene. Although the second LP/P does not seem to influence the disease course of DCM in patients and mice, the finding of a second LP/P can be of importance to their relatives.

[Left bundle branch block - dilated cardiomyopathy - heart failure: common links in the closed pathogenetic chain].

This review summarizes the available information on the epidemiology and prognosis of patients with left bundle branch block (LBBB), morphological alterations of the myocardium both resulting in and ensuing LBBB, cardiac biomechanics in LBBB, and possibilities of its correction.

Prevalence of HSPB6 gene variants in peripartum cardiomyopathy: Data from the German PPCM registry.

BACKGROUND: Heat shock protein family B (small) member 6 (HSPB6) mediates cardioprotective effects against stress-induced injury. In humans two gene variants of HSPB6 have been identified with a prevalence of 1% in patients with dilated cardiomyopathy (DCM). Peripartum cardiomyopathy (PPCM) is a potentially life-threatening heart disease of unknown etiology in previously healthy women of whom 16-20% of PPCM carry gene variants associated with cardiomyopathy. This study was designed to analyze the prevalence of pathogenic HSPB6 gene variants in PPCM. METHODS AND RESULTS: Whole-exome sequencing was performed in whole blood samples of PPCM patients (n = 65 PPCM patients from the German PPCM registry) and screened subsequently for HSPB6 gene variants. In this PPCM cohort one PPCM patient carries a HSPB6 gene variant of uncertain significance (VUS), which was not associated with changes in the amino acid sequence and no likely pathogenic or pathogenic variants were detected. CONCLUSION: HSPB6 gene variants did not occur more frequently in a cohort of PPCM patients from the German PPCM registry, compared to DCM patients. Genetic analyses in larger cohorts and in cohorts of different ethiologies of PPCM patients are needed to address the role of the genetic background in the pathogenesis of PPCM.

Contemporary aetiology of acute heart failure in a teaching hospital in Ghana.

BACKGROUND: Heart failure (HF) is recognized as a global public health disease associated with high morbidity and mortality. It is suggested that the main underlying causes of HF in developing countries differ from those identified in well-resourced countries. This study therefore presents the cardiovascular risk factors and the underlying aetiology of HF among admitted patients in a teaching Hospital in Ghana. METHOD: The study prospectively recruited 140 consecutive patients admitted for heart failure at the Medical department of the Korle-Bu Teaching Hospital from March to October, 2014. The study evaluated the cardiovascular risk factors and the aetiologies of heart failure, and compared the risk factors and aetiologies with patient's age and gender. RESULTS: The mean age of the study participants was 51.3 ± 16.8 years. The commonest cardiovascular risk factors observed were hypertension (46.5%), history of previous HF (40.7%), excessive alcohol use (38.6%), and family history of heart disease (29.3%); predominantly hypertension (68.3%). The major underlying aetiology of HF were dilated cardiomyopathy (38.6%), hypertensive heart disease (21.4%), ischaemic heart disease (13.6%) and valvular heart disease (12.9%). These underlying aetiology of HF were more common in patients aged 40 years and above (p = 0.004) and those presenting with multiple risk factors (p = 0.001). CONCLUSION: The major underlying aetiology of heart failure in adults were dilated cardiomyopathy, hypertensive heart disease, ischaemic heart disease and valvular heart disease, which were significantly high among patients aged 40 years and above and those presenting multiple risk factors. Hypertension, excessive alcohol use, family history of heart disease and personal history of previous heart failure diagnosis are noted as the main cardiovascular risk factors among heart failure patients.

Cardiomyopathy prevalence exceeds 30% in individuals with TTN variants and early atrial fibrillation.

PURPOSE: TTN truncating variants (TTNtvs) represent the largest known genetic cause of dilated cardiomyopathies (DCMs), however their penetrance for DCM in general populations is low. More broadly, patients with cardiomyopathies (CMs) often exhibit other cardiac conditions, such as atrial fibrillation (Afib), which has also been linked to TTNtvs. This retrospective analysis aims to characterize the relationship between different cardiac conditions in those with TTNtvs and identify individuals with the highest risk of DCM. METHODS: In this work we leverage longitudinal electronic health record and exome sequencing data from approximately 450,000 individuals in 2 health systems to statistically confirm and pinpoint the genetic footprint of TTNtv-related diagnoses aside from CM, such as Afib, and determine whether vetting additional significantly associated phenotypes better stratifies CM risk across those with TTNtvs. We focused on TTNtvs in exons with a percentage spliced in >90% (hiPSI TTNtvs), a representation of constitutive cardiac expression. RESULTS: When controlling for CM and Afib, other cardiac conditions retained only nominal association with TTNtvs. A sliding window analysis of TTNtvs across the locus confirms that the association is specific to hiPSI exons for both CM and Afib, with no meaningful associations in percent spliced in ≤90% exons (loPSI TTNtvs). The combination of hiPSI TTNtv status and early Afib diagnosis (before age 60) found a subset of TTNtv individuals at high risk for CM. The prevalence of CM in this subset was 33%, a rate that was 3.5 fold higher than that in individuals with hiPSI TTNtvs (9% prevalence), 5-fold higher than that in individuals without TTNtvs with early Afib (6% prevalence), and 80-fold higher than that in the general population. CONCLUSION: Our retrospective analyses revealed that those with hiPSI TTNtvs and early Afib (∼1/2900) have a high prevalence of CM (33%), far exceeding that in other individuals with TTNtvs and in those without TTNtvs with an early Afib diagnosis. These results show that combining phenotypic information along with genomic population screening can identify patients at higher risk for progressing to symptomatic heart failure.

Risk Factors and Prevalence of Dilated Cardiomyopathy in Sub-Saharan Africa: A Systematic Review.

Highlights  Prevalence of DCM varies widely in SSA.Cardiovascular risk factors are important in patients with DCM.The role of genetics in idiopathic DCM is not studied in major part of SSA.